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Establishment of a molecular genetic map of distal mouse chromosome 1: further definition of a conserved linkage group syntenic with human chromosome 1q.
Seldin, M F; Morse, H C; LeBoeuf, R C; Steinberg, A D
A linkage map of distal mouse chromosome 1 was constructed by restriction fragment length polymorphism analysis of DNAs from seven sets of recombinant inbred (RI) strains. The data obtained with seven probes on Southern hybridization combined with data from previous studies suggest the gene order Cfh, Pep-3/Ren-1,2, Ly-5, Lamb-2, At-3, Apoa-2/Ly-17,Spna-1. These results confirm and extend analyses of a large linkage group which includes genes present on a 20-30 cM span of mouse chromosome 1 and those localized to human chromosome 1q21-32. Moreover, the data indicate similar relative positions of human and mouse complement receptor-related genes REN, CD45, LAMB2, AT3, APOA2, and SPTA. These results suggest that mouse gene analyses may help in detailed mapping of human genes within such a syntenic group.
Tissue-specific expression of the human laminin alpha5-chain, and mapping of the gene to human chromosome 20q13.2-13.3 and to distal mouse chromosome 2 near the locus for the ragged (Ra) mutation
DEFF Research Database (Denmark)
Durkin, M E; Loechel, F; Mattei, M G
, heart, lung, skeletal muscle, kidney, and pancreas. The human laminin alpha5-chain gene (LAMA5) was assigned to chromosome 20q13.2-q13.3 by in situ hybridization, and the mouse gene (Lama5) was mapped by linkage analysis to a syntonic region of distal chromosome 2, close to the locus for the ragged (Ra...
Autosomal dominant distal myopathy: Linkage to chromosome 14
Energy Technology Data Exchange (ETDEWEB)
Laing, N.G.; Laing, B.A.; Wilton, S.D.; Dorosz, S.; Mastaglia, F.L.; Kakulas, B.A. [Australian Neuromuscular Research Institute, Perth (Australia); Robbins, P.; Meredith, C.; Honeyman, K.; Kozman, H.
We have studied a family segregating a form of autosomal dominant distal myopathy (MIM 160500) and containing nine living affected individuals. The myopathy in this family is closest in clinical phenotype to that first described by Gowers in 1902. A search for linkage was conducted using microsatellite, VNTR, and RFLP markers. In total, 92 markers on all 22 autosomes were run. Positive linkage was obtained with 14 of 15 markers tested on chromosome 14, with little indication of linkage elsewhere in the genome. Maximum two-point LOD scores of 2.60 at recombination fraction .00 were obtained for the markers MYH7 and D14S64 - the family structure precludes a two-point LOD score {ge} 3. Recombinations with D14S72 and D14S49 indicate that this distal myopathy locus, MPD1, should lie between these markers. A multipoint analysis assuming 100% penetrance and using the markers D14S72, D14S50, MYH7, D14S64, D14S54, and D14S49 gave a LOD score of exactly 3 at MYH7. Analysis at a penetrance of 80% gave a LOD score of 2.8 at this marker. This probable localization of a gene for distal myopathy, MPD1, on chromosome 14 should allow other investigators studying distal myopathy families to test this region for linkage in other types of the disease, to confirm linkage or to demonstrate the likely genetic heterogeneity. 24 refs., 3 figs., 1 tab.
The alpha-spectrin gene is on chromosome 1 in mouse and man.
Huebner, K; Palumbo, A P; Isobe, M; Kozak, C A; Monaco, S; Rovera, G; Croce, C M; Curtis, P J
By using alpha-spectrin cDNA clones of murine and human origin and somatic cell hybrids segregating either mouse or human chromosomes, the gene for alpha-spectrin has been mapped to chromosome 1 in both species. This assignment of the mouse alpha-spectrin gene to mouse chromosome 1 by DNA hybridization strengthens the previous identification of the alpha-spectrin locus in mouse with the sph locus, which previously was mapped by linkage analysis to mouse chromosome 1, distal to the Pep-3 locus. By in situ hybridization to human metaphase chromosomes, the human alpha-spectrin gene has been localized to 1q22-1q25; interestingly, the locus for a non-Rh-linked form of elliptocytosis has been provisionally mapped to band 1q2 by family linkage studies.
[Involvement of distal fragment of chromosome 13 in the regulation of sensitivity to ethanol in mice].
Bazovkina, D V; Kulikov, A V
The role of the fragment 57-65 cM of mouse chromosome 13 was studied in the regulation of ethanol action on locomotor activity, anxiety and sensitivity to hypnotic and hypothermic effects of ethanol. We used male mice of recombinant lines AKR/J and AKR.CBA-D13Mit76C, differing only in this fragment. After acute administration of ethanol only AKR mice showed the increase in the length of traveled distance in the open-field test (p mice demonstrated the increase the time spent in the center of open-field arena (p mice. The results suggest the involvement of the distal fragment 57-65 cM of chromosome 13 in the mechanisms of ethanol action in mice.
Mouse Chromosome Engineering for Modeling Human Disease
van der Weyden, Louise; Bradley, Allan
Chromosomal rearrangements occur frequently in humans and can be disease-associated or phenotypically neutral. Recent technological advances have led to the discovery of copy-number changes previously undetected by cytogenetic techniques. To understand the genetic consequences of such genomic changes, these mutations need to be modeled in experimentally tractable systems. The mouse is an excellent organism for this analysis because of its biological and genetic similarity to humans, and the e...
Linkage of genes for laminin B1 and B2 subunits on chromosome 1 in mouse.
Elliott, R W; Barlow, D; Hogan, B L
We have used cDNA clones for the B1 and B2 subunits of laminin to find restriction fragment length DNA polymorphisms for the genes encoding these polypeptides in the mouse. Three alleles were found for LamB2 and two for LamB1 among the inbred mouse strains. The segregation of these polymorphisms among recombinant inbred strains showed that these genes are tightly linked in the central region of mouse Chromosome 1 between Sas-1 and Ly-m22, 7.4 +/- 3.2 cM distal to the Pep-3 locus. There is no evidence in the mouse for pseudogenes for these proteins.
Sex reversal in the mouse (Mus musculus) is caused by a recurrent nonreciprocal crossover involving the x and an aberrant y chromosome.
Singh, L; Jones, K W
Satellite DNA (Bkm) from the W sex-determining chromosome of snakes, which is related to sequences on the mouse Y chromosome, has been used to analyze the DNA and chromosomes of sex-reversed (Sxr) XXSxr male mice. Such mice exhibit a male-specific Southern blot Bkm hybridization pattern, consistent with the presence of Y-chromosome DNA. In situ hybridization of Bkm to chromosomes of XXSxr mice shows an aberrant concentration of related sequences on the distal terminus of a large mouse chromosome. The XYSxr carrier male, however, shows a pair of small chromosomes, which are presumed to be aberrant Y derivatives. Meiosis in the XYSxr mouse involves transfer of chromatin rich in Bkm-related DNA from the Y-Y1 complex to the X distal terminus. We suggest that this event is responsible for the transmission of the Sxr trait.
Localization of the panhypopituitary dwarf mutation (df) on mouse chromosome 11 in an intersubspecific backcross.
Buckwalter, M S; Katz, R W; Camper, S A
Ames dwarf (df) is an autosomal recessive mutation characterized by severe dwarfism and infertility. This mutation provides a mouse model for panhypopituitarism. The dwarf phenotype results from failure in the differentiation of the cells which produce growth hormone, prolactin, and thyroid stimulating hormone. Using the backcross (DF/B-df/df X CASA/Rk) X DF/B-df/df, we confirmed the assignment of df to mouse chromosome 11 and demonstrated recombination between df and the growth hormone gene. This backcross is an invaluable resource for screening candidate genes for the df mutation. The df locus maps to less than 1 cM distal to Pad-1 (0.85 +/- 0.85 cM). Two new genes localized on mouse chromosome 11, Rpo2-1, and Edp-1, map to a region of conserved synteny with human chromosome 17. The localization of the alpha 1 adrenergic receptor, Adra-1, extends a known region of synteny conservation between mouse chromosome 11 and human chromosome 5, and suggests that a human counterpart to df would map to human chromosome 5.
Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17
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Cheng, S.V.; Nadeau, J.H.; Tanzi, R.E.; Watkins, P.C.; Jagadesh, J.; Taylor, B.A.; Haines, J.L.; Sacchi, N.; Gusella, J.F. (Harvard Medical School, Boston, MA (USA))
Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid {beta} precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, the authors have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS.
Comparative mapping of DNA markers from the familial Alzheimer disease and Down syndrome regions of human chromosome 21 to mouse chromosomes 16 and 17
International Nuclear Information System (INIS)
Cheng, S.V.; Nadeau, J.H.; Tanzi, R.E.; Watkins, P.C.; Jagadesh, J.; Taylor, B.A.; Haines, J.L.; Sacchi, N.; Gusella, J.F.
Mouse trisomy 16 has been proposed as an animal model of Down syndrome (DS), since this chromosome contains homologues of several loci from the q22 band of human chromosome 21. The recent mapping of the defect causing familial Alzheimer disease (FAD) and the locus encoding the Alzheimer amyloid β precursor protein (APP) to human chromosome 21 has prompted a more detailed examination of the extent of conservation of this linkage group between the two species. Using anonymous DNA probes and cloned genes from human chromosome 21 in a combination of recombinant inbred and interspecific mouse backcross analyses, the authors have established that the linkage group shared by mouse chromosome 16 includes not only the critical DS region of human chromosome 21 but also the APP gene and FAD-linked markers. Extending from the anonymous DNA locus D21S52 to ETS2, the linkage map of six loci spans 39% recombination in man but only 6.4% recombination in the mouse. A break in synteny occurs distal to ETS2, with the homologue of the human marker D21S56 mapping to mouse chromosome 17. Conservation of the linkage relationships of markers in the FAD region suggests that the murine homologue of the FAD locus probably maps to chromosome 16 and that detailed comparison of the corresponding region in both species could facilitate identification of the primary defect in this disorder. The break in synteny between the terminal portion of human chromosome 21 and mouse chromosome 16 indicates, however, that mouse trisomy 16 may not represent a complete model of DS
Chromosomal localization of the human and mouse hyaluronan synthase genes
Energy Technology Data Exchange (ETDEWEB)
Spicer, A.P.; McDonald, J.A. [Mayo Clinic Scottsdale, AZ (United States); Seldin, M.F. [Univ. of California Davis, CA (United States)] [and others
We have recently identified a new vertebrate gene family encoding putative hyaluronan (HA) synthases. Three highly conserved related genes have been identified, designated HAS1, HAS2, and HAS3 in humans and Has1, Has2, and Has3 in the mouse. All three genes encode predicted plasma membrane proteins with multiple transmembrane domains and approximately 25% amino acid sequence identity to the Streptococcus pyogenes HA synthase, HasA. Furthermore, expression of any one HAS gene in transfected mammalian cells leads to high levels of HA biosynthesis. We now report the chromosomal localization of the three HAS genes in human and in mouse. The genes localized to three different positions within both the human and the mouse genomes. HAS1 was localized to the human chromosome 19q13.3-q13.4 boundary and Has1 to mouse Chr 17. HAS2 was localized to human chromosome 8q24.12 and Has2 to mouse Chr 15. HAS3 was localized to human chromosome 16q22.1 and Has3 to mouse Chr 8. The map position for HAS1 reinforces the recently reported relationship between a small region of human chromosome 19q and proximal mouse chromosome 17. HAS2 mapped outside the predicted critical region delineated for the Langer-Giedion syndrome and can thus be excluded as a candidate gene for this genetic syndrome. 33 refs., 2 figs.
Neuropeptide Y receptor genes on human chromosome 4q31-q32 map to conserved linkage groups on mouse chromosomes 3 and 8
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Lutz, C.M.; Frankel, W.N. [Jackson Lab., Bar Harbor, ME (United States); Richards, J.E. [Univ. of Michigan Medical School, Ann Arbor, MI (United States)] [and others
Npy1r and Npy2r, the genes encoding mouse type 1 and type 2 neuropeptide Y receptors, have been mapped by interspecific backcross analysis. Previous studies have localized the human genes encoding these receptors to chromosome 4q31-q32. We have now assigned Npy1r and Npy2r to conserved linkage groups on mouse Chr 8 and Chr 3, respectively, which correspond to the distal region of human chromosome 4q. Using yeast artificial chromosomes, we have estimated the distance between the human genes to be approximately 6 cM. Although ancient tandem duplication events may account for some closely spaced G-protein-coupled receptor genes, the large genetic distance between the human type 1 and type 2 neuropeptide Y receptor genes raises questions about whether this mechanism accounts for their proximity. 20 refs., 1 fig.
Chromosomal variation in the house mouse
Czech Academy of Sciences Publication Activity Database
Piálek, Jaroslav; Hauffe, H. C.; Searle, J. B.
Roč. 84, č. 3 (2005), s. 535-563 ISSN 0024-4066. [The genus Mus as a model for evolutionary studies - a symposium in honour of Louis Thaler. Brno, 28.07.2003-30.07.2003] R&D Projects: GA AV ČR IAA6045601 Institutional research plan: CEZ:AV0Z6093917 Keywords : chromosomal evolution * hybrid zone * Robertsonian fusions Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.261, year: 2005
Appearance and evolution of the specific chromosomal rearrangements associated with malignant transformation of mouse m5S cells
International Nuclear Information System (INIS)
Kodama, S.; Okumura, Y.; Komatsu, K.; Sasaki, M.S.
Chromosomal alterations were studied during the acquisition of malignant phenotypes in two karyotypically distinct cells isolated from transformed foci induced by x-irradiation in mouse m5S cells. Because the transformants, despite foci origin, showed low ability to grow in agar, they were cultured in vitro with serial transfer schedules to allow further cell generations and assayed for anchorage independence (AI) at each passage level. The AI frequency increased with the cell doubling numbers. Chromosome analysis showed that a focus was one cell origin, but the transformants showed karyotypic instability during cell proliferation, giving rise to the rearrangements clustered in the distal region of the specific chromosomes. These rearrangements appeared to be directed toward the acquisition of malignant phenotypes. Analysis of the types and sites of rearrangements indicated that a mechanism exists that induces frequent rearrangements of the specific region of a chromosome during the process of transformation into the malignant state
Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.
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Maria Balcova
Full Text Available Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm and Mus m. domesticus (Mmd, it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2 genomic locus on Chromosome X (Chr X by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s responsible for variation in the global recombination rate between closely related mouse subspecies.
Hybrid Sterility Locus on Chromosome X Controls Meiotic Recombination Rate in Mouse.
Balcova, Maria; Faltusova, Barbora; Gergelits, Vaclav; Bhattacharyya, Tanmoy; Mihola, Ondrej; Trachtulec, Zdenek; Knopf, Corinna; Fotopulosova, Vladana; Chvatalova, Irena; Gregorova, Sona; Forejt, Jiri
Meiotic recombination safeguards proper segregation of homologous chromosomes into gametes, affects genetic variation within species, and contributes to meiotic chromosome recognition, pairing and synapsis. The Prdm9 gene has a dual role, it controls meiotic recombination by determining the genomic position of crossover hotspots and, in infertile hybrids of house mouse subspecies Mus m. musculus (Mmm) and Mus m. domesticus (Mmd), it further functions as the major hybrid sterility gene. In the latter role Prdm9 interacts with the hybrid sterility X 2 (Hstx2) genomic locus on Chromosome X (Chr X) by a still unknown mechanism. Here we investigated the meiotic recombination rate at the genome-wide level and its possible relation to hybrid sterility. Using immunofluorescence microscopy we quantified the foci of MLH1 DNA mismatch repair protein, the cytological counterparts of reciprocal crossovers, in a panel of inter-subspecific chromosome substitution strains. Two autosomes, Chr 7 and Chr 11, significantly modified the meiotic recombination rate, yet the strongest modifier, designated meiotic recombination 1, Meir1, emerged in the 4.7 Mb Hstx2 genomic locus on Chr X. The male-limited transgressive effect of Meir1 on recombination rate parallels the male-limited transgressive role of Hstx2 in hybrid male sterility. Thus, both genetic factors, the Prdm9 gene and the Hstx2/Meir1 genomic locus, indicate a link between meiotic recombination and hybrid sterility. A strong female-specific modifier of meiotic recombination rate with the effect opposite to Meir1 was localized on Chr X, distally to Meir1. Mapping Meir1 to a narrow candidate interval on Chr X is an important first step towards positional cloning of the respective gene(s) responsible for variation in the global recombination rate between closely related mouse subspecies.
Assignment of the Nance-Horan syndrome to the distal short arm of the X chromosome.
Zhu, D; Alcorn, D M; Antonarakis, S E; Levin, L S; Huang, P C; Mitchell, T N; Warren, A C; Maumenee, I H
There are three types of X-linked cataracts recorded in Mendelian Inheritance in Man (McKusick 1988): congenital total, with posterior sutural opacities in heterozygotes; congenital, with microcornea or slight microphthalmia; and the cataract-dental syndrome or Nance-Horan (NH) syndrome. To identify a DNA marker close to the gene responsible for the NH syndrome, linkage analysis on 36 members in a three-generation pedigree including seven affected males and nine carrier females was performed using 31 DNA markers. A LOD score of 1.662 at theta = 0.16 was obtained with probe 782 from locus DXS85 on Xp22.2-p22.3. Negative LOD scores were found at six loci on the short arm, one distal to DXS85, five proximal, and six probes spanning the long arm were highly negative. These results make the assignment of the locus for NH to the distal end of the short arm of the X chromosome likely.
Multiple mouse chromosomal loci for dynein-based motility
Energy Technology Data Exchange (ETDEWEB)
Vaughan, K.T.; Mikami, Atsushi; Paschal, B.M. [Worcester Foundation for Biomedical Research, Shrewsbury, MA (United States)] [and others
Dyneins are multisubunit mechanochemical enzymes capable of interacting with microtubules to generate force. Axonemal dyneins produce the motive force for ciliary and flagellar beating by inducing sliding between adjacent microtubules within the axoneme. Cytoplasmic dyneins translocate membranous organelles and chromosomes toward the minus ends of cytoplasmic microtubules. Dynactin is an accessory complex implicated in tethering cytoplasmic dynein to membranous organelles and mitotic kinetochores. In the studies described here, we have identified a number of new dynein genes and determined their mouse chromosomal locations by interspecific backcross analysis. We have also mapped several dynein and dynactin genes cloned previously. Our studies provide the first comprehensive attempt to map dynein and dynactin genes in mammals and provide a basis for the further analysis of dynein function in development and disease. 65 refs., 6 figs., 1 tab.
Molecular evidence for the induction of large interstitial deletions on mouse chromosome 8 by ionizing radiation
International Nuclear Information System (INIS)
Turker, Mitchell S.; Pieretti, Maura; Kumar, Sudha
The P19H22 mouse embryonal carcinoma cell line is characterized by a hemizygous deficiency for the chromosome 8 encoded aprt (adenine phosphoribosyltransferase) gene and heterozygosity for many chromosome 8 loci. We have previously demonstrated that this cell line is suitable for mutational studies because it is permissive of events ranging in size from base-pair substitutions at the aprt locus to apparent loss of chromosome 8. Large mutational events, defined by loss of the remaining aprt allele, were found to predominate in spontaneous mutants and those induced by ionizing radiation. In this study we have used a PCR based assay to screen for loss of heterozygosity at microsatellite loci both proximal and distal to aprt in 137 Cs-induced and spontaneous aprt mutants. This approach allowed us to distinguish apparent interstitial deletional events from apparent recombinational events. Significantly, 32.5% (26 of 80) of the mutational events induced by 137 Cs appeared to be interstitial deletions as compared with 7.7% (6 of 78) in the spontaneous group. This difference was statistically significant (p 137 Cs caused a significant number of deletion mutations. Most 137 Cs-induced interstitial deletions were larger than 6 cM, whereas none of the spontaneous deletions were larger than 6 cM. These results provide further support for the notion that ionizing radiation induces deletion mutations and validate the use of the P19H22 cell line for the study of events induced by ionizing radiation
NEUROD2 and NEUROD3 genes map to human chromosomes 17q12 and 5q23-q31 and mouse chromosomes 11 and 13, respectively
Energy Technology Data Exchange (ETDEWEB)
Tamimi, R.M.; Montgomery-Dyer, K.; Tapscott, S.J. [Fred Hutchinson Cancer Research Center, Seattle, WA (United States)] [and others
NEUROD2 and NEUROD3 are transcription factors involved in neurogenesis that are related to the basic helix-loop-helix protein NEUROD. NEUROD2 maps to human chromosome 17q12 and mouse chromosome 11. NEUROD3 maps to human chromosome 5q23-q31 and mouse chromosome 13. 16 refs., 2 figs.
Differential roles of stretch-sensitive pelvic nerve afferents innervating mouse distal colon and rectum
Feng, Bin; Brumovsky, Pablo R.; Gebhart, Gerald F.
Information about colorectal distension (i.e., colorectal dilation by increased intraluminal pressure) is primarily encoded by stretch-sensitive colorectal afferents in the pelvic nerve (PN). Despite anatomic differences between rectum and distal colon, little is known about the functional roles of colonic vs. rectal afferents in the PN pathway or the quantitative nature of mechanosensory encoding. We utilized an in vitro mouse colorectum-PN preparation to investigate pressure-encoding charac...
X chromosome control of meiotic chromosome synapsis in mouse inter-subspecific hybrids.
Directory of Open Access Journals (Sweden)
Tanmoy Bhattacharyya
Full Text Available Hybrid sterility (HS belongs to reproductive isolation barriers that safeguard the integrity of species in statu nascendi. Although hybrid sterility occurs almost universally among animal and plant species, most of our current knowledge comes from the classical genetic studies on Drosophila interspecific crosses or introgressions. With the house mouse subspecies Mus m. musculus and Mus m. domesticus as a model, new research tools have become available for studies of the molecular mechanisms and genetic networks underlying HS. Here we used QTL analysis and intersubspecific chromosome substitution strains to identify a 4.7 Mb critical region on Chromosome X (Chr X harboring the Hstx2 HS locus, which causes asymmetrical spermatogenic arrest in reciprocal intersubspecific F1 hybrids. Subsequently, we mapped autosomal loci on Chrs 3, 9 and 13 that can abolish this asymmetry. Combination of immunofluorescent visualization of the proteins of synaptonemal complexes with whole-chromosome DNA FISH on pachytene spreads revealed that heterosubspecific, unlike consubspecific, homologous chromosomes are predisposed to asynapsis in F1 hybrid male and female meiosis. The asynapsis is under the trans- control of Hstx2 and Hst1/Prdm9 hybrid sterility genes in pachynemas of male but not female hybrids. The finding concurred with the fertility of intersubpecific F1 hybrid females homozygous for the Hstx2(Mmm allele and resolved the apparent conflict with the dominance theory of Haldane's rule. We propose that meiotic asynapsis in intersubspecific hybrids is a consequence of cis-acting mismatch between homologous chromosomes modulated by the trans-acting Hstx2 and Prdm9 hybrid male sterility genes.
X chromosome control of meiotic chromosome synapsis in mouse inter-subspecific hybrids.
Bhattacharyya, Tanmoy; Reifova, Radka; Gregorova, Sona; Simecek, Petr; Gergelits, Vaclav; Mistrik, Martin; Martincova, Iva; Pialek, Jaroslav; Forejt, Jiri
Hybrid sterility (HS) belongs to reproductive isolation barriers that safeguard the integrity of species in statu nascendi. Although hybrid sterility occurs almost universally among animal and plant species, most of our current knowledge comes from the classical genetic studies on Drosophila interspecific crosses or introgressions. With the house mouse subspecies Mus m. musculus and Mus m. domesticus as a model, new research tools have become available for studies of the molecular mechanisms and genetic networks underlying HS. Here we used QTL analysis and intersubspecific chromosome substitution strains to identify a 4.7 Mb critical region on Chromosome X (Chr X) harboring the Hstx2 HS locus, which causes asymmetrical spermatogenic arrest in reciprocal intersubspecific F1 hybrids. Subsequently, we mapped autosomal loci on Chrs 3, 9 and 13 that can abolish this asymmetry. Combination of immunofluorescent visualization of the proteins of synaptonemal complexes with whole-chromosome DNA FISH on pachytene spreads revealed that heterosubspecific, unlike consubspecific, homologous chromosomes are predisposed to asynapsis in F1 hybrid male and female meiosis. The asynapsis is under the trans- control of Hstx2 and Hst1/Prdm9 hybrid sterility genes in pachynemas of male but not female hybrids. The finding concurred with the fertility of intersubpecific F1 hybrid females homozygous for the Hstx2(Mmm) allele and resolved the apparent conflict with the dominance theory of Haldane's rule. We propose that meiotic asynapsis in intersubspecific hybrids is a consequence of cis-acting mismatch between homologous chromosomes modulated by the trans-acting Hstx2 and Prdm9 hybrid male sterility genes.
X Chromosome Control of Meiotic Chromosome Synapsis in Mouse Inter-Subspecific Hybrids
Bhattacharyya, Tanmoy; Reifova, Radka; Gregorova, Sona; Simecek, Petr; Gergelits, Vaclav; Mistrik, Martin; Martincova, Iva; Pialek, Jaroslav; Forejt, Jiri
Hybrid sterility (HS) belongs to reproductive isolation barriers that safeguard the integrity of species in statu nascendi. Although hybrid sterility occurs almost universally among animal and plant species, most of our current knowledge comes from the classical genetic studies on Drosophila interspecific crosses or introgressions. With the house mouse subspecies Mus m. musculus and Mus m. domesticus as a model, new research tools have become available for studies of the molecular mechanisms and genetic networks underlying HS. Here we used QTL analysis and intersubspecific chromosome substitution strains to identify a 4.7 Mb critical region on Chromosome X (Chr X) harboring the Hstx2 HS locus, which causes asymmetrical spermatogenic arrest in reciprocal intersubspecific F1 hybrids. Subsequently, we mapped autosomal loci on Chrs 3, 9 and 13 that can abolish this asymmetry. Combination of immunofluorescent visualization of the proteins of synaptonemal complexes with whole-chromosome DNA FISH on pachytene spreads revealed that heterosubspecific, unlike consubspecific, homologous chromosomes are predisposed to asynapsis in F1 hybrid male and female meiosis. The asynapsis is under the trans- control of Hstx2 and Hst1/Prdm9 hybrid sterility genes in pachynemas of male but not female hybrids. The finding concurred with the fertility of intersubpecific F1 hybrid females homozygous for the Hstx2Mmm allele and resolved the apparent conflict with the dominance theory of Haldane's rule. We propose that meiotic asynapsis in intersubspecific hybrids is a consequence of cis-acting mismatch between homologous chromosomes modulated by the trans-acting Hstx2 and Prdm9 hybrid male sterility genes. PMID:24516397
CINcere Modelling : What Have Mouse Models for Chromosome Instability Taught Us?
Simon, Judith E; Bakker, Bjorn; Foijer, Floris
Chromosomal instability (CIN) is a process leading to errors in chromosome segregation and results in aneuploidy, a state in which cells have an abnormal number of chromosomes. CIN is a hallmark of cancer, and furthermore linked to ageing and age-related diseases such as Alzheimer's. Various mouse
Chromosome-wise dissection of the genome of the extremely big mouse line DU6i
M.R. Bevova (Marianna); Y.S. Aulchenko (Yurii); G. Aksu (Guzide); U. Renne (Ulla); K. Brockmann
textabstractThe extreme high-body-weight-selected mouse line DU6i is a polygenic model for growth research, harboring many small-effect QTL. We dissected the genome of this line into 19 autosomes and the Y chromosome by the construction of a new panel of chromosome substitution strains (CSS). The
Molecular and genetic characterization of a radiation-induced structural rearrangement in mouse chromosome 2 causing mutations at the limb deformity and agouti loci
International Nuclear Information System (INIS)
Woychik, R.P.; Generoso, W.M.; Russell, L.B.; Cain, K.T.; Cacheiro, N.L.; Bultman, S.J.; Selby, P.B.; Dickinson, M.E.; Hogan, B.L.
Molecular characterization of mutations in the mouse, particularly those involving agent-induced major structural alterations, is proving to be useful for correlating the structure and expression of individual genes with their function in the whole organism. Here we present the characterization of a radiation-induced mutation that simultaneously generated distinct alleles of both the limb deformity (ld) and agouti (a) loci, two developmentally important regions of chromosome 2 normally separated by 20 centimorgans. Cytogenetic analysis revealed that an interstitial segment of chromosome 17 (17B- 17C; or, possibly, 17A2-17B) had been translocated into the distal end of chromosome 2, resulting in a smaller-than-normal chromosome 17 (designated 17del) and a larger form of chromosome 2 designated 2(17). Additionally, a large interstitial segment of the 2(17) chromosome, immediately adjacent and proximal to the insertion site, did not match bands 2E4-2H1 at corresponding positions on a normal chromosome 2. Molecular analysis detected a DNA rearrangement in which a portion of the ld locus was joined to sequences normally tightly linked to the a locus. This result, along with the genetic and cytogenetic data, suggests that the alleles of ld and a in this radiation-induced mutation, designated ldIn2 and ajIn2, were associated with DNA breaks caused by an inversion of an interstitial segment in the 2(17) chromosome
CENP-A regulates chromosome segregation during the first meiosis of mouse oocytes.
Li, Li; Qi, Shu-Tao; Sun, Qing-Yuan; Chen, Shi-Ling
Proper chromosome separation in both mitosis and meiosis depends on the correct connection between kinetochores of chromosomes and spindle microtubules. Kinetochore dysfunction can lead to unequal distribution of chromosomes during cell division and result in aneuploidy, thus kinetochores are critical for faithful segregation of chromosomes. Centromere protein A (CENP-A) is an important component of the inner kinetochore plate. Multiple studies in mitosis have found that deficiencies in CENP-A could result in structural and functional changes of kinetochores, leading to abnormal chromosome segregation, aneuploidy and apoptosis in cells. Here we report the expression and function of CENP-A during mouse oocyte meiosis. Our study found that microinjection of CENP-A blocking antibody resulted in errors of homologous chromosome segregation and caused aneuploidy in eggs. Thus, our findings provide evidence that CENP-A is critical for the faithful chromosome segregation during mammalian oocyte meiosis.
Cytological localization of adenosine kinase, nucleoside phosphorylase-1, and esterase-10 genes on mouse chromosome 14
International Nuclear Information System (INIS)
Samuelson, L.C.; Farber, R.A.
The authors have determined the regional locations on mouse chromosome 14 of the genes for mouse adenosine kinase (ADK), nucleoside phosphorylase- 1 (NP-1), and esterase-10 (ES-10) by analysis of rearranged mouse chromosomes in gamma-irradiated Chinese hamster X mouse hybrid cell lines. Irradiated clones were screened for expression of the murine forms of these enzymes; segregant clones that expressed only one or two of the three markers were karyotyped. The patterns of enzyme expression in these segregants were correlated with the presence of rearranged chromosomes. The Adk gene was localized to bands A2 to B, Np-1 to bands B to C1, and Es-10 to bands D2 to E2
Sequence and chromosomal localization of the mouse brevican gene
DEFF Research Database (Denmark)
Rauch, U; Meyer, H; Brakebusch, C
Brevican is a brain-specific proteoglycan belonging to the aggrecan family. Phage clones containing the complete mouse brevican open reading frame of 2649 bp and the complete 3'-untranslated region of 341 bp were isolated from a mouse brain cDNA library, and cosmid clones containing the mouse...
Rheumatoid arthritis in an adult patient with mosaic distal 18q-, 18p- and ring chromosome 18 [version 2; referees: 2 approved
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Alanna Chau
Full Text Available Ring chromosome 18 has a highly variable phenotype, depending on the extent of distal arm deletions. It is most commonly presented as a combination of 18p- and distal 18q- syndrome. IgA deficiency and autoimmune diseases have been previously described in these patients. Seven cases of juvenile rheumatoid arthritis (JRA have been reported. Here we report the first case of late onset rheumatoid arthritis (RA in a 32 year old Dominican woman with hypothyroidism, vitiligo, IgA deficiency, interstitial lung disease (ILD, cystic bronchiectasis, and features consistent with ringed 18, 18p- and distal 18q syndrome. The multiple autoimmune findings in our patient lends further support to the idea of loci on chromosome 18 playing a role in autoimmune disease expression. Late onset RA and ILD in a patient with chromosome 18 abnormalities are novel findings and are additional conditions to be aware of in this population.
Changes in Nuclear Orientation Patterns of Chromosome 11 during Mouse Plasmacytoma Development
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Ann-Kristin Schmälter
Full Text Available Studying changes in nuclear architecture is a unique approach toward the understanding of nuclear remodeling during tumor development. One aspect of nuclear architecture is the orientation of chromosomes in the three-dimensional nuclear space. We studied mouse chromosome 11 in lymphocytes of [T38HxBALB/c]N mice with a reciprocal translocation between chromosome X and 11 (T38HT(X;11 exhibiting a long chromosome T(11;X and a short chromosome T(X;11 and in fast-onset plasmacytomas (PCTs induced in the same strain. We determined the three-dimensional orientation of chromosome 11 using a mouse chromosome 11 specific multicolor banding probe. We also examined the nuclear position of the small translocation chromosome T(X;11 which contains cytoband 11E2 and parts of E1. Chromosomes can point either with their centromeric or with their telomeric end toward the nuclear center or periphery, or their position is found in parallel to the nuclear border. In T38HT(X;11 nuclei, the most frequently observed orientation pattern was with both chromosomes 11 in parallel to the nuclear border ("PP". PCT cells showed nuclei with two or more copies of chromosome 11. In PCTs, the most frequent orientation pattern was with one chromosome in parallel and the other pointing with its centromeric end toward the nuclear periphery ("CP". There is a significant difference between the orientation patterns observed in T38HT(X;11 and in PCT nuclei (P < .0001.
Mapping of the bcl-2 oncogene on mouse chromosome 1.
Mock, B A; Givol, D; D'Hoostelaere, L A; Huppi, K; Seldin, M F; Gurfinkel, N; Unger, T; Potter, M; Mushinski, J F
Two bcl-2 alleles have been identified in inbred strains of mice by restriction fragment length polymorphism (RFLP). Analysis of a bcl-2 RFLP in a series of bilineal congenic strains (C.D2), developed as a tool for chromosomal mapping studies, revealed linkage of bcl-2 to the Idh-1/Pep-3 region of murine chromosome 1. The co-segregation of bcl-2 alleles with allelic forms of two other chromosome 1 loci, Ren-1,2 and Spna-1, in a set of back-cross progeny, positions bcl-2 7.8 cM centromeric from Ren-1,2.
Chromosomal mosaicism in mouse two-cell embryos after paternal exposure to acrylamide
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Marchetti, Francesco; Bishop, Jack; Lowe, Xiu; Wyrobek, Andrew J
Chromosomal mosaicism in human preimplantation embryos is a common cause ofspontaneous abortions, however, our knowledge of its etiology is limited. We used multicolor fluorescence in situ hybridization (FISH) painting to investigate whether paternally-transmitted chromosomal aberrations result in mosaicism in mouse 2-cell embryos. Paternal exposure to acrylamide, an important industrial chemical also found in tobacco smoke and generated during the cooking process of starchy foods, produced significant increases in chromosomally defective 2-cell embryos, however, the effects were transient primarily affecting the postmeiotic stages of spermatogenesis. Comparisons with our previous study of zygotes demonstrated similar frequencies of chromosomally abnormal zygotes and 2-cell embryos suggesting that there was no apparent selection against numerical or structural chromosomal aberrations. However, the majority of affected 2-cell embryos were mosaics showing different chromosomal abnormalities in the two blastomeric metaphases. Analyses of chromosomal aberrations in zygotes and 2-cell embryos showed a tendency for loss of acentric fragments during the first mitotic division ofembryogenesis, while both dicentrics and translocations apparently underwent propersegregation. These results suggest that embryonic development can proceed up to the end of the second cell cycle of development in the presence of abnormal paternal chromosomes and that even dicentrics can persist through cell division. The high incidence of chromosomally mosaic 2-cell embryos suggests that the first mitotic division of embryogenesis is prone to missegregation errors and that paternally-transmitted chromosomal abnromalities increase the risk of missegregation leading to embryonic mosaicism.
Two Y genes can replace the entire Y chromosome for assisted reproduction in the mouse.
Yamauchi, Yasuhiro; Riel, Jonathan M; Stoytcheva, Zoia; Ward, Monika A
The Y chromosome is thought to be important for male reproduction. We have previously shown that, with the use of assisted reproduction, live offspring can be obtained from mice lacking the entire Y chromosome long arm. Here, we demonstrate that live mouse progeny can also be generated by using germ cells from males with the Y chromosome contribution limited to only two genes, the testis determinant factor Sry and the spermatogonial proliferation factor Eif2s3y. Sry is believed to function primarily in sex determination during fetal life. Eif2s3y may be the only Y chromosome gene required to drive mouse spermatogenesis, allowing formation of haploid germ cells that are functional in assisted reproduction. Our findings are relevant, but not directly translatable, to human male infertility cases.
Meiotic drive on aberrant chromosome 1 in the mouse is determined by a linked distorter.
Agulnik, S I; Sabantsev, I D; Orlova, G V; Ruvinsky, A O
An aberrant chromosome 1 carrying an inverted fragment with two amplified DNA regions was isolated from wild populations of Mus musculus. Meiotic drive favouring the aberrant chromosome was demonstrated for heterozygous females. Its cause was preferential passage of aberrant chromosome 1 to the oocyte. Genetic analysis allowed us to identify a two-component system conditioning deviation from equal segregation of the homologues. The system consists of a postulated distorter and responder. The distorter is located on chromosome 1 distally to the responder, between the ln and Pep-3 genes, and it acts on the responder when in trans position. Polymorphism of the distorters was manifested as variation in their effect on meiotic drive level in the laboratory strain and mice from wild populations.
Imaging of Chromosome Dynamics in Mouse Testis Tissue by Immuno-FISH.
Scherthan, Harry
The mouse (Mus musculus) represents the central mammalian genetic model system for biomedical and developmental research. Mutant mouse models have provided important insights into chromosome dynamics during the complex meiotic differentiation program that compensates for the genome doubling at fertilization. Homologous chromosomes (homologues) undergo dynamic pairing and recombine during first meiotic prophase before they become partitioned into four haploid sets by two consecutive meiotic divisions that lack an intervening S-phase. Fluorescence in situ hybridization (FISH) has been instrumental in the visualization and imaging of the dynamic reshaping of chromosome territories and mobility during prophase I, in which meiotic telomeres were found to act as pacemakers for the chromosome pairing dance. FISH combined with immunofluorescence (IF) co-staining of nuclear proteins has been instrumental for the visualization and imaging of mammalian meiotic chromosome behavior. This chapter describes FISH and IF methods for the analysis of chromosome dynamics in nuclei of paraffin-embedded mouse testes. The techniques have proven useful for fresh and archived paraffin testis material of several mammalian species.
Nuclear Architecture of Mouse Spermatocytes: Chromosome Topology, Heterochromatin, and Nucleolus.
Berrios, Soledad
The nuclear organization of spermatocytes in meiotic prophase I is primarily determined by the synaptic organization of the bivalents that are bound by their telomeres to the nuclear envelope and described as arc-shaped trajectories through the 3D nuclear space. However, over this basic meiotic organization, a spermatocyte nuclear architecture arises that is based on higher-ordered patterns of spatial associations among chromosomal domains from different bivalents that are conditioned by the individual characteristics of chromosomes and the opportunity for interactions between their domains. Consequently, the nuclear architecture is species-specific and prone to modification by chromosomal rearrangements. This model is valid for the localization of any chromosomal domain in the meiotic prophase nucleus. However, constitutive heterochromatin plays a leading role in shaping nuclear territories. Thus, the nuclear localization of nucleoli depends on the position of NORs in nucleolar bivalents, but the association among nucleolar chromosomes mainly depends on the presence of constitutive heterochromatin that does not affect the expression of the ribosomal genes. Constitutive heterochromatin and nucleoli form complex nuclear territories whose distribution in the nuclear space is nonrandom, supporting the hypothesis regarding the existence of a species-specific nuclear architecture in first meiotic prophase spermatocytes. © 2017 S. Karger AG, Basel.
Chromosomal instability in mouse embryonic fibroblasts null for the transcriptional co-repressor Ski
Marcelain, Katherine; Armisen, Ricardo; Aguirre, Adam; Ueki, Nobuhide; Toro, Jessica; Colmenares, Clemencia; Hayman, Michael J
Ski is a transcriptional regulator that has been considered an oncoprotein, given its ability to induce oncogenic transformation in avian model systems. However, studies in mouse and in some human tumor cells have also indicated a tumor suppressor activity for this protein. We found that Ski−/− mouse embryo fibroblasts exhibit high levels of genome instability, namely aneuploidy, consistent with a tumor suppressor function for Ski. Time-lapse microscopy revealed lagging chromosomes and chroma...
A Turner Syndrome Patient Carrying a Mosaic Distal X Chromosome Marker
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Roberto L. P. Mazzaschi
Full Text Available A skin sample from a 17-year-old female was received for routine karyotyping with a set of clinical features including clonic seizures, cardiomyopathy, hepatic adenomas, and skeletal dysplasia. Conventional karyotyping revealed a mosaic Turner syndrome karyotype with a cell line containing a small marker of X chromosome origin. This was later confirmed on peripheral blood cultures by conventional G-banding, fluorescence in situ hybridisation and microarray analysis. Similar Turner mosaic marker chromosome cases have been previously reported in the literature, with a variable phenotype ranging from the mild "classic" Turner syndrome to anencephaly, agenesis of the corpus callosum, complex heart malformation, and syndactyly of the fingers and toes. This case report has a phenotype that is largely discordant with previously published cases as it lies at the severe end of the Turner variant phenotype scale. The observed cytogenetic abnormalities in this study may represent a coincidental finding, but we cannot exclude the possibility that the marker has a nonfunctioning X chromosome inactivation locus, leading to functional disomy of those genes carried by the marker.
Characterization of a panel of somatic cell hybrids for regional mapping of the mouse X chromosome
International Nuclear Information System (INIS)
Avner, P.; Arnaud, D.; Amar, L.; Cambrou, J.; Winking, H.; Russell, L.B.
A panel of five hybrid cell lines containing mouse X chromosomes with various deletions has been obtained by fusing splenocytes from male mice carrying one of a series of reciprocal X-autosome translocations with the azaguanine-resistant Chinese hamster cell line CH3g. These hybrids have been extensively characterized by using the allozymes hypoxanthine/guanine phosphoribosyltransferase (encoded by the Hprt locus) and α-galactosidase (Ags) and a series of 11 X-chromosome-specific DNA probes whose localization had been previously established by linkage studies. Such studies have established the genetic breakpoints of the T(X;12)13R1 and T(X;2)14R1 X-autosome translocations on the X chromosome and provided additional information as to the X-chromosome genetic breakpoints of the T(X;16)16H, T(X;4)7R1, and T(X;7)6R1 translocations. The data establish clearly that both the T(X;7)5RI and T(X;12)13R1 X-chromosome breakpoints are proximal to Hprt, the breakpoint of the former being more centromeric, lying as it does in the 9-centimorgan interval between the ornithine transcarbamoylase (Otc) and DXPas7 (M2C) loci. These five hybrid cell lines provide, with the previously characterized EBS4 hybrid cell line, a nested series of seven mapping intervals distributed along the length of the mouse X chromosome. Their characterization not only allows further correlation of the genetic and cytological X-chromosome maps but also should permit the rapid identification of DNA probes specific for particular regions of the mouse X chromosome
Chromosomal integrity of freeze-dried mouse spermatozoa after 137Cs γ-ray irradiation
International Nuclear Information System (INIS)
Kusakabe, Hirokazu; Kamiguchi, Yujiroh
This study demonstrated that freeze-dried mouse spermatozoa possess strong resistance to 137 Cs γ-ray irradiation at doses of up to 8 Gy. Freeze-dried mouse spermatozoa were rehydrated and injected into mouse oocytes with an intracytoplasmic sperm injection (ICSI) technique. Most oocytes can be activated after ICSI by using spermatozoa irradiated with γ-rays before and after freeze-drying. Sperm chromosome complements were analyzed at the first cleavage metaphase. Chromosome aberrations increased in a dose-dependent manner in the spermatozoa irradiated before freeze-drying. However, no increase in oocytes with chromosome aberrations was observed when fertilized by spermatozoa that had been irradiated after freeze-drying, as compared with freeze-dried spermatozoa that had not been irradiated. These results suggest that both the chromosomal integrity of freeze-dried spermatozoa, as well as their ability to activate oocytes, were protected from γ-ray irradiation at doses at which chromosomal damage is found to be strongly induced in spermatozoa suspended in solution
Non-homologous chromosome synapsis during mouse meiosis : consequences for male fertility and survival of progeny
Peters, A.H.F.M.
In the mouse, heterozygosity for several reciprocal and Robertsonian translocations is associated with impairment of chromosome synapsis and suppression of crossover formation in segments near the points of exchange during prophase of meiosis. This thesis describes the analysis of the consequences
Chromosome preparations from microplate cultures of man, dog, rat, and mouse
de Jong, B; Anders, GJPA; van der Meer, Ingrid H
A simple method for making chromosomal preparations from 105 leukocytes from man, dog, mouse, and rat and from 0.01 ml total human and dog blood is developed. The leukocytes and the peripheral blood are cultured in Cooke microtiter plates in a culture volume of 0.1 ml. The culture medium is R.P.M.I.
MURCS Association with Partial Duplication of the Distal Long Chromosome 5 and Unilateral Ovarian Agenesis
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Anna Dabkowska-Huc
Full Text Available A combination of the congenital abnormalities, Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia, is defined as the MURCS association. Various genetic defects have been described in the MURCS association so far, yet the unambiguous molecular basis of these disorders has not been established. We report the case of an 18-year-old woman who presented with primary amenorrhea, right kidney, Arnold-Chiari malformation, and Klippel-Feil syndrome. In addition, the patient showed the following unusual features: right ovarian and Skenes gland agenesis, cubitus valgus with hyperextension and decreased range of motion at elbows, and facial changes. Moreover, the performed DNA analysis showed interstitial duplication in chromosome 5 (5q35.1. In the duplicated region, there are genes whose function is not well known. It is thought that they have an influence on the early stages of development and their joining in the later period can lead to neoplastic disorders, especially leukemias.
Chromosome-wise dissection of the genome of the extremely big mouse line DU6i.
Bevova, Marianna R; Aulchenko, Yurii S; Aksu, Soner; Renne, Ulla; Brockmann, Gudrun A
The extreme high-body-weight-selected mouse line DU6i is a polygenic model for growth research, harboring many small-effect QTL. We dissected the genome of this line into 19 autosomes and the Y chromosome by the construction of a new panel of chromosome substitution strains (CSS). The DU6i chromosomes were transferred to a DBA/2 mice genetic background by marker-assisted recurrent backcrossing. Mitochondria and the X chromosome were of DBA/2 origin in the backcross. During the construction of these novel strains, >4000 animals were generated, phenotyped, and genotyped. Using these data, we studied the genetic control of variation in body weight and weight gain at 21, 42, and 63 days. The unique data set facilitated the analysis of chromosomal interaction with sex and parent-of-origin effects. All analyzed chromosomes affected body weight and weight gain either directly or in interaction with sex or parent of origin. The effects were age specific, with some chromosomes showing opposite effects at different stages of development.
Chromosomal localization of the gonadotropin-releasing hormone receptor gene to human chromosome 4q13. 1-q21. 1 and mouse chromosome 5
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Kaiser, U.B.; Dushkin, H.; Beier, D.R.; Chin, W.W. (Harvard Medical School, Boston, MA (United States)); Altherr, M.R. (Los Alamos National Lab., NM (United States))
The gonadotropin-releasing hormone receptor (GRHR) is a G-protein-coupled receptor on the cell surface of pituitary gonadotropes, where it serves to transduce signals from the extracellular ligand, the hypothalamic factor gonadotropin-releasing hormone, and to modulate the synthesis and secretion of luteinizing hormone and follicle-stimulating hormone. The authors have localized the GRHR gene to the q13.1-q21.1 region of the human chromosome 4 using mapping panels of human/rodent somatic cell hybrids containing different human chromosomes or different regions of human chromosome 4. Furthermore, using linkage analysis of single-strand conformational polymorphisms, the murine GRHR gene was localized to mouse chromosome 5, linked to the endogenous retroviral marker Pmv-11. This is consistent with the evolutionary conservation of homology between these two regions, as has been previously suggested from comparative mapping of several other loci. The localization of the GRHR gene may be useful in the study of disorders of reproduction. 22 refs., 2 figs.
... St Louis, MO: Elsevier; 2017:chap 69. Taber's Medical Dictionary Online. Chromosome. www.tabers.com/tabersonline/view/Tabers-Dictionary/753321/all/chromosome?q=Chromosome&ti=0 . Accessed June 11, 2017.
X chromosome control of meiotic chromosome synapsis in mouse inter-subspecific hybrids
Czech Academy of Sciences Publication Activity Database
Bhattacharyya, Tanmoy; Reifová, R.; Gregorová, Soňa; Šimeček, Petr; Gergelits, Václav; Mistrik, M.; Martincová, Iva; Piálek, Jaroslav; Forejt, Jiří
Roč. 10, č. 2 (2014), e1004088 ISSN 1553-7404 R&D Projects: GA AV ČR Premium Academiae of the Academy of Sciences of the Czech Republic; GA MŠk(CZ) LD11079; GA ČR GA206/08/0640; GA MŠk ED1.1.00/02.0109 Institutional support: RVO:68081766 ; RVO:68378050 Keywords : hybrid sterility * meiotic asynapsis * chromosome substitution strains Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 8.167, year: 2013
Establishment of a mouse model with misregulated chromosome condensation due to defective Mcph1 function.
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Marc Trimborn
Full Text Available Mutations in the human gene MCPH1 cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC in early G2 phase and delayed decondensation post-mitosis (PCC syndrome. The gene encodes the BRCT-domain containing protein microcephalin/BRIT1. Apart from its role in the regulation of chromosome condensation, the protein is involved in the cellular response to DNA damage. We report here on the first mouse model of impaired Mcph1-function. The model was established based on an embryonic stem cell line from BayGenomics (RR0608 containing a gene trap in intron 12 of the Mcph1 gene deleting the C-terminal BRCT-domain of the protein. Although residual wild type allele can be detected by quantitative real-time PCR cell cultures generated from mouse tissues bearing the homozygous gene trap mutation display the cellular phenotype of misregulated chromosome condensation that is characteristic for the human disorder, confirming defective Mcph1 function due to the gene trap mutation. While surprisingly the DNA damage response (formation of repair foci, chromosomal breakage, and G2/M checkpoint function after irradiation appears to be largely normal in cell cultures derived from Mcph1(gt/gt mice, the overall survival rates of the Mcph1(gt/gt animals are significantly reduced compared to wild type and heterozygous mice. However, we could not detect clear signs of premature malignant disease development due to the perturbed Mcph1 function. Moreover, the animals show no obvious physical phenotype and no reduced fertility. Body and brain size are within the range of wild type controls. Gene expression on RNA and protein level did not reveal any specific pattern of differentially regulated genes. To the best of our knowledge this represents the first mammalian transgenic model displaying a defect in mitotic chromosome condensation and is also the first mouse model for impaired Mcph1-function.
Establishment of a mouse model with misregulated chromosome condensation due to defective Mcph1 function.
Trimborn, Marc; Ghani, Mahdi; Walther, Diego J; Dopatka, Monika; Dutrannoy, Véronique; Busche, Andreas; Meyer, Franziska; Nowak, Stefanie; Nowak, Jean; Zabel, Claus; Klose, Joachim; Esquitino, Veronica; Garshasbi, Masoud; Kuss, Andreas W; Ropers, Hans-Hilger; Mueller, Susanne; Poehlmann, Charlotte; Gavvovidis, Ioannis; Schindler, Detlev; Sperling, Karl; Neitzel, Heidemarie
Mutations in the human gene MCPH1 cause primary microcephaly associated with a unique cellular phenotype with premature chromosome condensation (PCC) in early G2 phase and delayed decondensation post-mitosis (PCC syndrome). The gene encodes the BRCT-domain containing protein microcephalin/BRIT1. Apart from its role in the regulation of chromosome condensation, the protein is involved in the cellular response to DNA damage. We report here on the first mouse model of impaired Mcph1-function. The model was established based on an embryonic stem cell line from BayGenomics (RR0608) containing a gene trap in intron 12 of the Mcph1 gene deleting the C-terminal BRCT-domain of the protein. Although residual wild type allele can be detected by quantitative real-time PCR cell cultures generated from mouse tissues bearing the homozygous gene trap mutation display the cellular phenotype of misregulated chromosome condensation that is characteristic for the human disorder, confirming defective Mcph1 function due to the gene trap mutation. While surprisingly the DNA damage response (formation of repair foci, chromosomal breakage, and G2/M checkpoint function after irradiation) appears to be largely normal in cell cultures derived from Mcph1(gt/gt) mice, the overall survival rates of the Mcph1(gt/gt) animals are significantly reduced compared to wild type and heterozygous mice. However, we could not detect clear signs of premature malignant disease development due to the perturbed Mcph1 function. Moreover, the animals show no obvious physical phenotype and no reduced fertility. Body and brain size are within the range of wild type controls. Gene expression on RNA and protein level did not reveal any specific pattern of differentially regulated genes. To the best of our knowledge this represents the first mammalian transgenic model displaying a defect in mitotic chromosome condensation and is also the first mouse model for impaired Mcph1-function.
Comparative mapping in the beige-satin region of mouse chromosome 13
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Perou, C.M.; Pryor, R.; Kaplan, J. [Univ. of Utah School of Medicine, Salt Lake City, UT (United States)] [and others
The proximal end of mouse chromosome (Chr) 13 contains regions conserved on human chromosomes 1q42-q44, 6p23-p21, and 7p22-p13. This region also contains mutations that may be models for human disease, including beige (human Chediak-Higashi syndrome). An interspecific backcross of SB/Le and Mus spretus mice was used to generate a molecular genetic linkage map of mouse chromosome 13 with an emphasis on the proximal region including beige (bg) and satin (sa). This map provides the gene order of the two phenotypic markers bg and sa relative to restriction fragment length polymorphisms and simple sequence length polymorphisms in 131 backcross animals. In parallel, we have created a physical map of the region using Nidogen (Nid) as a molecular starting point for cloning a YAC contig that was used to identify the beige gene. The physical map provides the fine-structure order of genes and anonymous DNA fragments that was not resolved by the genetic linkage mapping. The results show that the bg region of mouse Chr 13 is highly conserved on human Chr 1q42-q44 and provide a starting point for a complete functional analysis of the entire bg-sa interval. 37 refs., 4 figs., 1 tab.
Essential roles of BCCIP in mouse embryonic development and structural stability of chromosomes.
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Huimei Lu
Full Text Available BCCIP is a BRCA2- and CDKN1A(p21-interacting protein that has been implicated in the maintenance of genomic integrity. To understand the in vivo functions of BCCIP, we generated a conditional BCCIP knockdown transgenic mouse model using Cre-LoxP mediated RNA interference. The BCCIP knockdown embryos displayed impaired cellular proliferation and apoptosis at day E7.5. Consistent with these results, the in vitro proliferation of blastocysts and mouse embryonic fibroblasts (MEFs of BCCIP knockdown mice were impaired considerably. The BCCIP deficient mouse embryos die before E11.5 day. Deletion of the p53 gene could not rescue the embryonic lethality due to BCCIP deficiency, but partially rescues the growth delay of mouse embryonic fibroblasts in vitro. To further understand the cause of development and proliferation defects in BCCIP-deficient mice, MEFs were subjected to chromosome stability analysis. The BCCIP-deficient MEFs displayed significant spontaneous chromosome structural alterations associated with replication stress, including a 3.5-fold induction of chromatid breaks. Remarkably, the BCCIP-deficient MEFs had a ∼20-fold increase in sister chromatid union (SCU, yet the induction of sister chromatid exchanges (SCE was modestly at 1.5 fold. SCU is a unique type of chromatid aberration that may give rise to chromatin bridges between daughter nuclei in anaphase. In addition, the BCCIP-deficient MEFs have reduced repair of irradiation-induced DNA damage and reductions of Rad51 protein and nuclear foci. Our data suggest a unique function of BCCIP, not only in repair of DNA damage, but also in resolving stalled replication forks and prevention of replication stress. In addition, BCCIP deficiency causes excessive spontaneous chromatin bridges via the formation of SCU, which can subsequently impair chromosome segregations in mitosis and cell division.
Complex distal 10q rearrangement in a girl with mild intellectual disability: follow up of the patient and review of the literature of non-acrocentric satellited chromosomes.
Sarri, Catherine; Douzgou, Sofia; Gyftodimou, Yolanda; Tümer, Zeynep; Ravn, Kirstine; Pasparaki, Angela; Sarafidou, Theologia; Kontos, Harry; Kokotas, Haris; Karadima, Georgia; Grigoriadou, Maria; Pandelia, Effie; Theodorou, Virginia; Moschonas, Nicholas K; Petersen, Michael B
We report on an intellectually disabled girl with a de novo satellited chromosome 10 (10qs) and performed a review of the literature of the non-acrocentric satellited chromosomes (NASC). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited non-acrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is, to our knowledge, the third report of a 10qs chromosome. The phenotype observed in the proband prompted a search for a structural rearrangement of chromosome 10q. By microsatellite analysis we observed a 4 Mb deletion on the long arm of chromosome 10, approximately 145 kb from the telomere. FISH and array CGH analyses revealed a complex rearrangement involving in range from the centromere to the telomere: A 9.64 Mb 10q26.11-q26.2 duplication, a 1.3 Mb region with no copy number change, followed by a 5.62 Mb 10q26.2-q26.3 deletion and a translocation of satellite material. The homology between the repeat sequences at 10q subtelomere region and the sequences on the acrocentric short arms may explain the origin of the rearrangement and it is likely that the submicroscopic microdeletion and microduplication are responsible for the abnormal phenotype in our patient. The patient presented here, with a 15-year follow-up, manifests a distinct phenotype different from the 10q26 pure distal monosomy and trisomy syndromes. Copyright © 2011 Wiley Periodicals, Inc.
Chromosomal instability in mouse embryonic fibroblasts null for the transcriptional co-repressor Ski.
Marcelain, Katherine; Armisen, Ricardo; Aguirre, Adam; Ueki, Nobuhide; Toro, Jessica; Colmenares, Clemencia; Hayman, Michael J
Ski is a transcriptional regulator that has been considered an oncoprotein given its ability to induce oncogenic transformation in avian model systems. However, studies in mouse and in some human tumor cells have also indicated a tumor suppressor activity for this protein. We found that Ski-/- mouse embryo fibroblasts exhibit high levels of genome instability, namely aneuploidy, consistent with a tumor suppressor function for Ski. Time-lapse microscopy revealed lagging chromosomes and chromatin/chromosome bridges as the major cause of micronuclei (MN) formation and the subsequent aneuploidy. Although these cells arrested in mitosis after treatment with spindle disrupting drugs and exhibited a delayed metaphase/anaphase transition, spindle assembly checkpoint (SAC) was not sufficient to prevent chromosome missegregation, consistent with a weakened SAC. Our in vivo analysis also showed dynamic metaphase plate rearrangements with switches in polarity in cells arrested in metaphase. Importantly, after ectopic expression of Ski the cells that displayed this metaphase arrest died directly during metaphase or after aberrant cell division, relating SAC activation and mitotic cell death. This increased susceptibility to undergo mitosis-associated cell death reduced the number of MN-containing cells. The presented data support a new role for Ski in the mitotic process and in maintenance of genetic stability, providing insights into the mechanism of tumor suppression mediated by this protein. Copyright © 2011 Wiley Periodicals, Inc.
Eccentric localization of catalase to protect chromosomes from oxidative damages during meiotic maturation in mouse oocytes.
Park, Yong Seok; You, Seung Yeop; Cho, Sungrae; Jeon, Hyuk-Joon; Lee, Sukchan; Cho, Dong-Hyung; Kim, Jae-Sung; Oh, Jeong Su
The maintenance of genomic integrity and stability is essential for the survival of every organism. Unfortunately, DNA is vulnerable to attack by a variety of damaging agents. Oxidative stress is a major cause of DNA damage because reactive oxygen species (ROS) are produced as by-products of normal cellular metabolism. Cells have developed eloquent antioxidant defense systems to protect themselves from oxidative damage along with aerobic metabolism. Here, we show that catalase (CAT) is present in mouse oocytes to protect the genome from oxidative damage during meiotic maturation. CAT was expressed in the nucleus to form unique vesicular structures. However, after nuclear envelope breakdown, CAT was redistributed in the cytoplasm with particular focus at the chromosomes. Inhibition of CAT activity increased endogenous ROS levels, but did not perturb meiotic maturation. In addition, CAT inhibition produced chromosomal defects, including chromosome misalignment and DNA damage. Therefore, our data suggest that CAT is required not only to scavenge ROS, but also to protect DNA from oxidative damage during meiotic maturation in mouse oocytes.
Clathrin heavy chain 1 is required for spindle assembly and chromosome congression in mouse oocytes.
Zhao, Jie; Wang, Lu; Zhou, Hong-Xia; Liu, Li; Lu, Angeleem; Li, Guang-Peng; Schatten, Heide; Liang, Cheng-Guang
Clathrin heavy chain 1 (CLTC) has been considered a "moonlighting protein" which acts in membrane trafficking during interphase and in stabilizing spindle fibers during mitosis. However, its roles in meiosis, especially in mammalian oocyte maturation, remain unclear. This study investigated CLTC expression and function in spindle formation and chromosome congression during mouse oocyte meiotic maturation. Our results showed that the expression level of CLTC increased after germinal vesicle breakdown (GVBD) and peaked in the M phase. Immunostaining results showed CLTC distribution throughout the cytoplasm in a cell cycle-dependent manner. Appearance and disappearance of CLTC along with β-tubulin (TUBB) could be observed during spindle dynamic changes. To explore the relationship between CLTC and microtubule dynamics, oocytes at metaphase were treated with taxol or nocodazole. CLTC colocalized with TUBB at the enlarged spindle and with cytoplasmic asters after taxol treatment; it disassembled and distributed into the cytoplasm along with TUBB after nocodazole treatment. Disruption of CLTC function using stealth siRNA caused a decreased first polar body extrusion rate and extensive spindle formation and chromosome congression defects. Taken together, these results show that CLTC plays an important role in spindle assembly and chromosome congression through a microtubule correlation mechanism during mouse oocyte maturation.
TRPV3, a thermosensitive channel is expressed in mouse distal colon epithelium
International Nuclear Information System (INIS)
Ueda, Takashi; Yamada, Takahiro; Ugawa, Shinya; Ishida, Yusuke; Shimada, Shoichi
The thermo-transient receptor potential (thermoTRP) subfamily is composed of channels that are important in nociception and thermo-sensing. Here, we show a selective expression of TRPV3 channel in the distal colon throughout the gastrointestinal tract. Expression analyses clearly revealed that TRPV3 mRNA and proteins were expressed in the superficial epithelial cells of the distal colon, but not in those of the stomach, duodenum or proximal colon. In a subset of primary epithelial cells cultured from the distal colon, carvacrol, an agonist for TRPV3, elevated cytosolic Ca 2+ concentration in a concentration-dependent manner. This response was inhibited by ruthenium red, a TRPV channel antagonist. Organotypic culture supported that the carvacrol-responsive cells were present in superficial epithelial cells. Moreover, application of carvacrol evoked ATP release in primary colonic epithelial cells. We conclude that TRPV3 is present in absorptive cells in the distal colon and may be involved in a variety of cellular functions.
Protective effects of vitamins C and E against γ-ray-induced chromosomal damage in mouse
International Nuclear Information System (INIS)
Sarma, L.; Kesavan, P.C.
The effects of vitamins C and E on bone marrow chromosomes of the mouse exposed to 1 Gy of whole-body γ-irradiation were studied. These vitamins, dissolved in water/peanut oil, were administered orally as acute doses, either 2 h before, immediately after, or 2 h after irradiation. Both vitamins significantly reduced the frequencies of micronuclei and chromosomal aberrations in bone marrow cells; radioprotection by vitamin E was, however, appreciably greater than that afforded by vitamin C. Administration of the vitamins to mice immediately after irradiation was as effective as that 2 h before irradiation. A sequential treatment consisting of both the vitamins did not result in additional radioprotection over that afforded by vitamin E alone. The probable mechanisms of radioprotection are discussed. (author)
Hypermutability of mouse chromosome 2 during the development of x-ray-induced murine myeloid leukemia
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Rithidech, K.; Bond, V.P.; Cronkite, E.P.; Thompson, M.H.; Bullis, J.E.
In an effort to identify the precise role of a deletion at regions D-E of mouse chromosome 2 [del2(D-E)] during the development of radiation-induced myeloid leukemia, we conducted a serial sacrifice study in which metaphase chromosomes were examined by the G-banding technique. Such metaphase cells were collected from x-irradiated mice during the period of transformation of some of the normal hematopoietic cells to the fully developed leukemic phenotype. A group of 250 CBA/Ca male mice (10-12 weeks old) were exposed to a single dose of 2 Gy of 250-kilovolt-peak x-rays; 42 age-matched male mice served as controls. Groups of randomly selected mice were sacrificed at 20 hr, 1 week, and then at intervals of 3 months up to 24 months after x-irradiation. Slides for cytogenetic, hematological, and histological examination were prepared for each animal at each sacrifice time. The majority of such lesions were translocations at 2F or 2H, strongly suggesting hyper mutability of these sites on mouse chromosome 2. No lesions were found in control mice. The finding leads to the possibility that genomic lesions close to 2D and 2E are aberrants associated with radiation leukemogenesis, whereas a single clone of cells with a del2(D-E) may lead directly to overt leukemia. The data also indicate that leukemic transformation arises from the cumulative effects of multiple genetic events on chromosome 2, reinforcing the thesis that multiple steps of mutation occur in the pathogenesis of cancer. 15 refs., 1 fig., 2 tabs
A molecular deletion of distal chromosome 4p in two families with a satellited chromosome 4 lacking the Wolf-Hirschhorn syndrome phenotype.
Estabrooks, L L; Lamb, A N; Kirkman, H N; Callanan, N P; Rao, K W
We report two families with a satellited chromosome 4 short arm (4ps). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited nonacrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is the first report of 4ps chromosomes. Our families are remarkable in that both unaffected and affected individuals carry the 4ps chromosome. The phenotypes observed in affected individuals, although dissimilar, were sufficient to encourage a search for a deletion of chromosome 4p. By Southern blot analysis and fluorescence in situ hybridization, a deletion of material mapping approximately 150 kb from chromosome 4pter was discovered. This deletion is notable because it does not result in the Wolf-Hirschhorn syndrome and can result in an apparently normal phenotype. We speculate that homology between subterminal repeat sequences on 4p and sequences on the acrocentric short arms may explain the origin of the rearrangement and that position effect may play a role in the expression of the abnormal phenotype.
Dissection of a locus on mouse chromosome 5 reveals arthritis promoting and inhibitory genes
DEFF Research Database (Denmark)
Lindvall, Therese; Karlsson, Jenny; Holmdahl, Rikard
with Eae39 congenic- and sub-interval congenic mice, carrying RIIIS/J genes on the B10.RIII genetic background, revealed three loci within Eae39 that control disease and anti-collagen antibody titers. Two of the loci promoted disease and the third locus was protecting from collagen induced arthritis...... development. By further breeding of mice with small congenic fragments, we identified a 3.2 Megabasepair (Mbp) interval that regulates disease. CONCLUSIONS: Disease promoting- and protecting genes within the Eae39 locus on mouse chromosome 5, control susceptibility to collagen induced arthritis. A disease......-protecting locus in the telomeric part of Eae39 results in lower anti-collagen antibody responses. The study shows the importance of breeding sub-congenic mouse strains to reveal genetic effects on complex diseases....
Three loci on mouse chromosome 5 and 10 modulate sex determination in XX Ods/+ mice.
Poirier, Christophe; Moran, Jennifer L; Kovanci, Ertug; Petit, Deborah C; Beier, David R; Bishop, Colin E
In mouse, XY embryos are committed to the male sex determination pathway after the transient expression of the Y-linked Sry gene in the Sertoli cell lineage between 10.5 and 12.5 dpc. In the C57BL/6J strain, male sex determination program can be modulated by some autosomal genes. The C57BL/6J alleles at these autosomal loci can antagonize male sex determination in combination with specific Sry alleles. In this report, the authors have identified an effect of these C57BL/6J specific alleles in combination with a mutated Sox9 allele, Sox9(Ods). Authors report the mapping of three of these genetic loci on mouse chromosome 5 and 10 in a backcross of the Ods mutation to the C57BL/6J background. Our study confirms the importance of the strain C57BL/6J for the investigation of the genetic mechanisms that control sex determination.
Physical mapping of a large plant genome using global high-information-content-fingerprinting: the distal region of the wheat ancestor Aegilops tauschii chromosome 3DS
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You Frank M
Full Text Available Abstract Background Physical maps employing libraries of bacterial artificial chromosome (BAC clones are essential for comparative genomics and sequencing of large and repetitive genomes such as those of the hexaploid bread wheat. The diploid ancestor of the D-genome of hexaploid wheat (Triticum aestivum, Aegilops tauschii, is used as a resource for wheat genomics. The barley diploid genome also provides a good model for the Triticeae and T. aestivum since it is only slightly larger than the ancestor wheat D genome. Gene co-linearity between the grasses can be exploited by extrapolating from rice and Brachypodium distachyon to Ae. tauschii or barley, and then to wheat. Results We report the use of Ae. tauschii for the construction of the physical map of a large distal region of chromosome arm 3DS. A physical map of 25.4 Mb was constructed by anchoring BAC clones of Ae. tauschii with 85 EST on the Ae. tauschii and barley genetic maps. The 24 contigs were aligned to the rice and B. distachyon genomic sequences and a high density SNP genetic map of barley. As expected, the mapped region is highly collinear to the orthologous chromosome 1 in rice, chromosome 2 in B. distachyon and chromosome 3H in barley. However, the chromosome scale of the comparative maps presented provides new insights into grass genome organization. The disruptions of the Ae. tauschii-rice and Ae. tauschii-Brachypodium syntenies were identical. We observed chromosomal rearrangements between Ae. tauschii and barley. The comparison of Ae. tauschii physical and genetic maps showed that the recombination rate across the region dropped from 2.19 cM/Mb in the distal region to 0.09 cM/Mb in the proximal region. The size of the gaps between contigs was evaluated by comparing the recombination rate along the map with the local recombination rates calculated on single contigs. Conclusions The physical map reported here is the first physical map using fingerprinting of a complete
Chromosome breakage in Prader-Willi and Angelman syndrome deletions may involve recombination between a repeat at the proximal and distal breakpoints
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Amos-Landgraf J.; Nicholls, R.D. [Case Western Reserve Univ., Cleveland, OH (United States); Gottlieb, W. [Univ. of Florida, Gainesville, FL (United States)] [and others
Prader-Willi (PWS) and Angelman (AS) syndromes most commonly arise from large deletions of 15q11-q13. Deletions in PWS are paternal in origin, while those in AS are maternal in origin, clearly demonstrating genomic imprinting in these clinically distinct neurobehavioural disorders. In at least 90% of PWS and AS deletion patients, the same 4 Mb region within 15q11-q13 is deleted with breakpoints clustering in single YAC clones at the proximal and distal ends. To study the mechanism of chromosome breakage in PWS and AS, we have previously isolated 25 independent clones from these three YACs using Alu-vector PCR. Four clones were selected that appear to detect a low copy repeat that is located in the proximal and distal breakpoint regions of chromosome 15q11-q13. Three clones detect the same 4 HindIII bands in genomic DNA, all from 15q11-q13, with differing intensities for the probes located at the proximal or distal breakpoints region, respectively. This suggests that these probes detect related members of a low-copy repeat at either location. Moreover, the 254RL2 probe detects a novel HindIII band in two unrelated PWS deletion patients, suggesting that this may represent a breakpoint fragment, with recombination occurring within a similar interval in both patients. A fourth clone, 318RL3 detects 5 bands in HindIII-digested genomic DNA, all from 15q11-q13. This YAC endclone itself is not deleted in PWS and AS deletion patients, as seen by an invariant strong band. Two other strong bands are variably intact or deleted in different PWS or AS deletion patients, suggesting a relationship of this sequence to the breakpoints. Moreover, PCR using 318RL3 primers from the distal 93C9 YAC led to the isolation of a related clone with 96% identity, demonstrating the existence of a low-copy repeat with members close to the proximal and distal breakpoints. Taken together, our data suggest a complex, low-copy repeat with members at both the proximal and distal boundaries.
Tet Enzymes Regulate Telomere Maintenance and Chromosomal Stability of Mouse ESCs
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Jiao Yang
Full Text Available Ten-eleven translocation (Tet family proteins convert 5-methylcytosine to 5-hydroxymethylcytosine. We show that mouse embryonic stem cells (ESCs depleted of Tet1 and/or Tet2 by RNAi exhibit short telomeres and chromosomal instability, concomitant with reduced telomere recombination. Tet1 and Tet2 double-knockout ESCs also display short telomeres but to a lesser extent. Notably, Tet1/2/3 triple-knockout ESCs show heterogeneous telomere lengths and increased frequency of telomere loss and chromosomal fusion. Mechanistically, Tets depletion or deficiency increases Dnmt3b and decreases 5hmC levels, resulting in elevated methylation levels at sub-telomeres. Consistently, knockdown of Dnmt3b or addition of 2i (MAPK and GSK3β inhibitors, which also inhibits Dnmt3b, reduces telomere shortening, partially rescuing Tet1/2 deficiency. Interestingly, Tet1/2 double or Tet1/2/3 triple knockout in ESCs consistently upregulates Zscan4, which may counteract telomere shortening. Together, Tet enzymes play important roles in telomere maintenance and chromosomal stability of ESCs by modulating sub-telomeric methylation levels.
Chromosome alterations in the X-ray-induced transformants of cultured mouse cell line
International Nuclear Information System (INIS)
Kodama, Seiji; Komatsu, Kenshi; Okumura, Yutaka; Sasaki, M.S.
Mouse m5S cells were subjected to soft X-ray irradiation. Twenty-four transformants were separated as indicators of focus formation. Two clones, cl.4103 and cl.6310, were chosen for the analysis of chromosome alterations in transformants. A parent strain, m5S/1M, served as the control. Anchorage independence (AG) was not detected in the control strain, irrespective of culture conditions and population doubling number (PDN). In the case of transformants, the frequency of AG was increased with increasing PDN for cl.4103, and was constant for cl.6310, irrespective of PDN. Karyotype of m5S/1M was 42, X, -Y, +der (6) t(6;13), t(8;8), +8, +15. In addition, -13, der(10) and -der(6)t(6;13), der(5), +mar occurred as karyotype alterations for cl.4103 and cl. 6310, respectively. The present experiment indicated that chromosome alterations secondary to primary alterations occur in a high frequency in the transforming process of X-ray irradiated cells, and that the secondary chromosome alterations result in selective proliferation of transformed clones. (Namekawa, K)
A genetic map of mouse chromosome 1 near the Lsh-Ity-Bcg disease resistance locus.
Mock, B; Krall, M; Blackwell, J; O'Brien, A; Schurr, E; Gros, P; Skamene, E; Potter, M
Isozyme and restriction fragment length polymorphism (RFLP) analyses of backcross progeny, recombinant inbred strains, and congenic strains of mice positioned eight genetic markers with respect to the Lsh-Ity-Bcg disease resistance locus. Allelic isoforms of Idh-1 and Pep-3 and RFLPs detected by Southern hybridization for Myl-1, Cryg, Vil, Achrg, bcl-2, and Ren-1,2, between BALB/cAnPt and DBA/2NPt mice, were utilized to examine the cosegregation of these markers with the Lsh-Ity-Bcg resistance phenotype in 103 backcross progeny. An additional 47 backcross progeny from a cross between C57BL/10ScSn and B10.L-Lshr/s mice were examined for the cosegregation of Myl-1 and Vil RFLPs with Lsh phenotypic differences. Similarly, BXD recombinant inbred strains were typed for RFLPs upon hybridization with Vil and Achrg. Recombination frequencies generated in the different test systems were statistically similar, and villin (Vil) was identified as the molecular marker closest (1.7 +/- 0.8 cM) to the Lsh-Ity-Bcg locus. Two other DNA sequences, nebulin (Neb) and an anonymous DNA fragment (D2S3), which map to a region of human chromosome 2q that is homologous to proximal mouse chromosome 1, were not closely linked to the Lsh-Ity-Bcg locus. This multipoint linkage analysis of chromosome 1 surrounding the Lsh-Ity-Bcg locus provides a basis for the eventual isolation of the disease gene.
Characterization of the chromosomal inversion associated with the Koa mutation in the mouse revealed the cause of skeletal abnormalities
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Suzuki Hiroetsu
Full Text Available Abstract Background Koala (Koa is a dominant mutation in mice causing bushy muzzle and pinna, and is associated with a chromosomal inversion on the distal half of chromosome 15. To identify the gene responsible for the Koa phenotypes, we investigated phenotypes of Koa homozygous mice and determined the breakpoints of the inversion with a genetic method using recombination between two different chromosomal inversions. Results Skeletal preparation of Koa homozygotes showed marked deformity of the ribs and a wider skull with extended zygomatic arches, in addition to a general reduction in the lengths of long bones. They also had open eyelids at birth caused by a defect in the extension of eyelid anlagen during the embryonic stages. The proximal and distal breakpoints of the Koa inversion were determined to be 0.8-Mb distal to the Trsps1 gene and to 0.1-Mb distal to the Hoxc4 gene, respectively, as previously reported. The phenotypes of mice with the recombinant inverted chromosomes revealed the localization of the gene responsible the Koa phenotype in the vicinity of the proximal recombinant breakpoint. Expression of the Trsps1 gene in this region was significantly reduced in the Koa homozygous and heterozygous embryos. Conclusion While no gene was disrupted by the chromosomal inversion, an association between the Koa phenotype and the proximal recombinant breakpoint, phenotypic similarities with Trps1-deficient mice or human patients with TRSP1 mutations, and the reduced expression of the Trsps1 gene in Koa mice, indicated that the phenotypes of the Koa mice are caused by the altered expression of the Trps1 gene.
No significant effect of monosomy for distal 21q22. 3 on the Down syndrom phenotype in mirror' duplications of chromosome 21
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Pangalos, C.; Prieur, M.; Rethore, M.O.; Lejeune, J. (Institut de Progenese, Paris (France)); Theophile, D.; Sinet, P.M.; Chettouh, Z.; Delabar, J.M. (Hopital Necker Enfants Malades, Paris (France)); Marks, A. (Univ. of Toronto, Ontario (Canada)); Stamboulieh-Abazis, D. (Diagnostic Genetic Center, Athens (Greece)); Verellen, C. (Centre de Genetique Humaine, Brussels (Belgium))
Three Down syndrome patients for whom karyotypic analysis showed a mirror' (reverse tandem) duplication of chromosome 21 were studied by phenotypic, cytogenetic, and molecular methods. On high-resolution R-banding analysis performed in two cases, the size of the fusion 21q22.3 band was apparently less than twice the size of the normal 21q22.3, suggesting a partial deletion of distal 21q. The evaluation of eight chromosome 21 single-copy sequences of the 21q22 region - namely, SOD1, D21S15, D21S42, CRYA1, PFKL, CD18, COL6A1, and S100B - by a slot blot method showed in all three cases a partial deletion of 21q22.3 and partial monosomy. The translocation breakpoints were different in each patient, and in two cases the rearranged chromosome was found to be asymmetrical. The molecular definition of the monosomy 21 in each patient was, respectively, COL6A1-S100B, CD18-S100B, and PFKL-S100B. DNA polymorphism analysis indicated in all cases a homozygosity of the duplicated material. The duplicated region was maternal in two patients and paternal in one patient. These data suggest that the reverse tandem chromosomes did not result from a telomeric fusion between chromosomes 21 but from a translocation between sister chromatids. The phenotypes of these patients did not differ significantly from that of individuals with full trisomy 21, except in one case with large ears with an unfolded helix. The fact that monosomy of distal 21q22.3 in these patients resulted in a phenotype very similar to Down syndrome suggests that the duplication of the genes located in this part of chromosome 21 is not necessary for the pathogenesis of the Down syndrome features observed in these patients, including most of the facial and hand features, muscular hypotonia, cardiopathy of the Fallot tetralogy type, and part of the mental retardation. 54 refs., 5 figs., 3 tabs.
Mlh1 deficiency in normal mouse colon mucosa associates with chromosomally unstable colon cancer
Pussila, Marjaana; Törönen, Petri; Einarsdottir, Elisabet; Katayama, Shintaro; Krjutškov, Kaarel; Holm, Liisa; Kere, Juha; Peltomäki, Päivi; Mäkinen, Markus J; Linden, Jere; Nyström, Minna
Abstract Colorectal cancer (CRC) genome is unstable and different types of instabilities, such as chromosomal instability (CIN) and microsatellite instability (MSI) are thought to reflect distinct cancer initiating mechanisms. Although 85% of sporadic CRC reveal CIN, 15% reveal mismatch repair (MMR) malfunction and MSI, the hallmarks of Lynch syndrome with inherited heterozygous germline mutations in MMR genes. Our study was designed to comprehensively follow genome-wide expression changes and their implications during colon tumorigenesis. We conducted a long-term feeding experiment in the mouse to address expression changes arising in histologically normal colonic mucosa as putative cancer preceding events, and the effect of inherited predisposition (Mlh1+/−) and Western-style diet (WD) on those. During the 21-month experiment, carcinomas developed mainly in WD-fed mice and were evenly distributed between genotypes. Unexpectedly, the heterozygote (B6.129-Mlh1tm1Rak) mice did not show MSI in their CRCs. Instead, both wildtype and heterozygote CRC mice showed a distinct mRNA expression profile and shortage of several chromosomal segregation gene-specific transcripts (Mlh1, Bub1, Mis18a, Tpx2, Rad9a, Pms2, Cenpe, Ncapd3, Odf2 and Dclre1b) in their colon mucosa, as well as an increased mitotic activity and abundant numbers of unbalanced/atypical mitoses in tumours. Our genome-wide expression profiling experiment demonstrates that cancer preceding changes are already seen in histologically normal colon mucosa and that decreased expressions of Mlh1 and other chromosomal segregation genes may form a field-defect in mucosa, which trigger MMR-proficient, chromosomally unstable CRC. PMID:29701748
CRISPR reveals a distal super-enhancer required for Sox2 expression in mouse embryonic stem cells.
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Yan Li
Full Text Available The pluripotency of embryonic stem cells (ESCs is maintained by a small group of master transcription factors including Oct4, Sox2 and Nanog. These core factors form a regulatory circuit controlling the transcription of a number of pluripotency factors including themselves. Although previous studies have identified transcriptional regulators of this core network, the cis-regulatory DNA sequences required for the transcription of these key pluripotency factors remain to be defined. We analyzed epigenomic data within the 1.5 Mb gene-desert regions around the Sox2 gene and identified a 13kb-long super-enhancer (SE located 100kb downstream of Sox2 in mouse ESCs. This SE is occupied by Oct4, Sox2, Nanog, and the mediator complex, and physically interacts with the Sox2 locus via DNA looping. Using a simple and highly efficient double-CRISPR genome editing strategy we deleted the entire 13-kb SE and characterized transcriptional defects in the resulting monoallelic and biallelic deletion clones with RNA-seq. We showed that the SE is responsible for over 90% of Sox2 expression, and Sox2 is the only target gene along the chromosome. Our results support the functional significance of a SE in maintaining the pluripotency transcription program in mouse ESCs.
The landscape of chromosomal aberrations in breast cancer mouse models reveals driver-specific routes to tumorigenesis
Ben-David, Uri; Ha, Gavin; Khadka, Prasidda; Jin, Xin; Wong, Bang; Franke, Lude; Golub, Todd R.
Aneuploidy and copy-number alterations (CNAs) are a hallmark of human cancer. Although genetically engineered mouse models (GEMMs) are commonly used to model human cancer, their chromosomal landscapes remain underexplored. Here we use gene expression profiles to infer CNAs in 3,108 samples from 45
Biotin-deficient diet induces chromosome misalignment and spindle defects in mouse oocytes.
Tsuji, Ai; Nakamura, Toshinobu; Shibata, Katsumi
Increased abnormal oocytes due to meiotic chromosome misalignment and spindle defects lead to elevated rates of infertility, miscarriage, and trisomic conceptions. Here, we investigated the effect of biotin deficiency on oocyte quality. Three-week-old female ICR mice were fed a biotin-deficient or control diet (0, 0.004 g biotin/kg diet) for 21 days. On day 22, these mouse oocytes were analyzed by immunofluorescence. Due to biotin, undernutrition increased the frequency of abnormal oocytes (the biotin deficient vs. control: 40 vs. 16%). Next, the remaining mice in the biotin-deficient group were fed a control or biotin-deficient diet from day 22 to 42. Although biotin nutritional status in the recovery group was restored, the frequency of abnormal oocytes in the recovery group was still higher than that in the control group (48 vs. 18%). Our results indicate that steady, sufficient biotin intake is required for the production of high-quality oocytes in mice.
Dominant hemimelia and En-1 on mouse chromosome 1 are not allelic.
Higgins, M; Hill, R E; West, J D
Previous studies have shown that En-1, a homeobox-containing gene, maps close to or at the Dh locus in the mouse. Since homeobox-containing genes are key genes in the control of development the close proximity of En-1 to the developmentally significant gene Dh raised the possibility that the Dh mutation represented a mutant allele of En-1. A genetic analysis involving En-1, Dh, and other chromosome 1 markers (Emv-17, ln and Pep-3) shows that although Dh and En-1 are closely linked they are separable by recombination (4/563). The likely gene order and recombination frequencies of these loci are: ln (5.2 +/- 0.9) Emv-17 (1.1 +/- 0.4) Dh (0.7 +/- 0.4) En-1 (3.0 +/- 0.7) Pep-3. This shows that Dh is not a mutant allele of En-1.
A genetic basis for a postmeiotic X versus Y chromosome intragenomic conflict in the mouse.
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Julie Cocquet
Full Text Available Intragenomic conflicts arise when a genetic element favours its own transmission to the detriment of others. Conflicts over sex chromosome transmission are expected to have influenced genome structure, gene regulation, and speciation. In the mouse, the existence of an intragenomic conflict between X- and Y-linked multicopy genes has long been suggested but never demonstrated. The Y-encoded multicopy gene Sly has been shown to have a predominant role in the epigenetic repression of post meiotic sex chromatin (PMSC and, as such, represses X and Y genes, among which are its X-linked homologs Slx and Slxl1. Here, we produced mice that are deficient for both Sly and Slx/Slxl1 and observed that Slx/Slxl1 has an opposite role to that of Sly, in that it stimulates XY gene expression in spermatids. Slx/Slxl1 deficiency rescues the sperm differentiation defects and near sterility caused by Sly deficiency and vice versa. Slx/Slxl1 deficiency also causes a sex ratio distortion towards the production of male offspring that is corrected by Sly deficiency. All in all, our data show that Slx/Slxl1 and Sly have antagonistic effects during sperm differentiation and are involved in a postmeiotic intragenomic conflict that causes segregation distortion and male sterility. This is undoubtedly what drove the massive gene amplification on the mouse X and Y chromosomes. It may also be at the basis of cases of F1 male hybrid sterility where the balance between Slx/Slxl1 and Sly copy number, and therefore expression, is disrupted. To the best of our knowledge, our work is the first demonstration of a competition occurring between X and Y related genes in mammals. It also provides a biological basis for the concept that intragenomic conflict is an important evolutionary force which impacts on gene expression, genome structure, and speciation.
Colocalization of somatic and meiotic double strand breaks near the Myc oncogene on mouse chromosome 15.
Ng, Siemon H; Maas, Sarah A; Petkov, Petko M; Mills, Kevin D; Paigen, Kenneth
Both somatic and meiotic recombinations involve the repair of DNA double strand breaks (DSBs) that occur at preferred locations in the genome. Improper repair of DSBs during either mitosis or meiosis can lead to mutations, chromosomal aberration such as translocations, cancer, and/or cell death. Currently, no model exists that explains the locations of either spontaneous somatic DSBs or programmed meiotic DSBs or relates them to each other. One common class of tumorigenic translocations arising from DSBs is chromosomal rearrangements near the Myc oncogene. Myc translocations have been associated with Burkitt lymphoma in humans, plasmacytoma in mice, and immunocytoma in rats. Comparing the locations of somatic and meiotic DSBs near the mouse Myc oncogene, we demonstrated that the placement of these DSBs is not random and that both events clustered in the same short discrete region of the genome. Our work shows that both somatic and meiotic DSBs tend to occur in proximity to each other within the Myc region, suggesting that they share common originating features. It is likely that some regions of the genome are more susceptible to both somatic and meiotic DSBs, and the locations of meiotic hotspots may be an indicator of genomic regions more susceptible to DNA damage. (c) 2009 Wiley-Liss, Inc.
A major locus on mouse chromosome 18 controls XX sex reversal in Odd Sex (Ods) mice.
Qin, Yangjun; Poirier, Christophe; Truong, Cavatina; Schumacher, Armin; Agoulnik, Alexander I; Bishop, Colin E
We have previously reported a dominant mouse mutant, Odd sex (Ods), in which XX Ods/+ mice on the FVB/N background show complete sex reversal, associated with expression of Sox9 in the fetal gonads. Remarkably, when crossed to the A/J strain approximately 95% of the (AXFVB) F(1) XX Ods/+ mice developed as fully fertile, phenotypic females, the remainder developing as males or hermaphrodites. Using a (AXFVB) F(2) population, we conducted a genome-wide linkage scan to identify the number and chromosomal location of potential Ods modifier genes. A single major locus termed Odsm1 was mapped to chromosome 18, tightly linked to D18Mit189 and D18Mit210. Segregation at this locus could account for the presence of sex reversal in 100% of XX Ods/+ mice which develop as males, for the absence of sex reversal in approximately 92% of XX Ods/+ mice which develop as females, and for the mixed sexual phenotype in approximately 72% of XX Ods/+ mice that develop with ambiguous genitalia. We propose that homozygosity for the FVB-derived allele strongly favors Ods sex reversal, whereas homozygosity for the A/J-derived allele inhibits it. In mice heterozygous at Odsm1, the phenotypic outcome, male, female or hermaphrodite, is determined by a complex interaction of several minor modifying loci. The close proximity of Smad2, Smad7 and Smad4 to D18Mit189/210 provides a potential mechanism through which Odsm1 might act.
Brahmarasayana protects against Ethyl methanesulfonate or Methyl methanesulfonate induced chromosomal aberrations in mouse bone marrow cells
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Guruprasad Kanive
Full Text Available Abstract Background Ayurveda, the traditional Indian system of medicine has given great emphasis to the promotion of health. Rasayana is one of the eight branches of Ayurveda which refers to rejuvenant therapy. It has been reported that rasayanas have immuno-modulatory, antioxidant and antitumor functions, however, the genotoxic potential and modulation of DNA repair of many rasayanas have not been evaluated. Methods The present study assessed the role of Brahmarasayana (BR on Ethyl methanesulfonate (EMS-and Methyl methanesulfonate (MMS-induced genotoxicity and DNA repair in in vivo mouse test system. The mice were orally fed with BR (5 g or 8 mg / day for two months and 24 h later EMS or MMS was given intraperitoneally. The genotoxicity was analyzed by chromosomal aberrations, sperm count, and sperm abnormalities. Results The results have revealed that BR did not induce significant chromosomal aberrations when compared to that of the control animals (p >0.05. On the other hand, the frequencies of chromosomal aberrations induced by EMS (240 mg / kg body weight or MMS (125 mg / kg body weight were significantly higher (p Conclusion The effect of BR, as it relates to antioxidant activity was not evident in liver tissue however rasayana treatment was observed to increase constitutive DNA base excision repair and reduce clastogenicity. Whilst, the molecular mechanisms of such repair need further exploration, this is the first report to demonstrate these effects and provides further evidence for the role of brahmarasayana in the possible improvement of quality of life.
The human thyroglobulin gene: a polymorphic marker localized distal to C-MYC on chromosome 8 band q24
Baas, F.; Bikker, H.; Geurts van Kessel, A.; Melsert, R.; Pearson, P. L.; de Vijlder, J. J.; van Ommen, G. J.
The human thyroglobulin (Tg) gene is localized to chromosome 8 and regionally to band q24 as shown independently by both in situ hybridization techniques and Southern blot analysis of human-rodent somatic cell hybrids. Analysis of hybrids derived from a Burkitt lymphoma, with a translocation
Detection of obesity QTLs on mouse chromosomes 1 and 7 by selective DNA pooling
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Taylor, B.A.; Phillips, S.J. [Jackson Lab., Bar Harbor, ME (United States)
The inheritance of obesity has been analyzed in an intercross between the lean 129/Sv mouse strain and the obesity-prone EL/Suz mouse strain. The weights of three major fat pads were determined on 4-month-old mice, and the sum of these weights, divided by body weight, was used as an adiposity index. The strategy of selective DNA pooling was used as a primary screen to identify putative quantitative trait loci (QTLs) affecting adiposity index. DNA pools representing the leanest 15% and fattest 15% of the F2 progeny were compared for differential allelic enrichment using widely dispersed microsatellite variants. To evaluate putative QTLs, individual genotyping and interval mapping were employed to estimate QTL effects and assess statistical significance. One QTL affecting adiposity index, which accounted for 12.3% of phenotypic variance in gender-merged data, was mapped to the central region of Chromosome (Chr) 7. The QTL allele inherited from EL conferred increased adiposity. A second QTL that accounts for 6.3% of phenotypic variance was identified on Chr 1 near D1Mitt211. At both QTLs, the data are consistent with dominant inheritance of the allele contributing to obesity. The possible relationships between these QTLs and previously described obesity QYLs, major obesity mutations, and candidate genes are discussed. 42 refs., 3 figs., 3 tabs.
Structural organization and chromosomal assignment of the mouse embryonic TEA domain-containing factor (ETF) gene.
Suzuki, K; Yasunami, M; Matsuda, Y; Maeda, T; Kobayashi, H; Terasaki, H; Ohkubo, H
Embryonic TEA domain-containing factor (ETF) belongs to the family of proteins structurally related to transcriptional enhancer factor-1 (TEF-1) and is implicated in neural development. Isolation and characterization of the cosmid clones encoding the mouse ETF gene (Etdf) revealed that Etdf spans approximately 17.9 kb and consists of 12 exons. The exon-intron structure of Etdf closely resembles that of the Drosophila scalloped gene, indicating that these genes may have evolved from a common ancestor. The multiple transcription initiation sites revealed by S1 protection and primer extension analyses are consistent with the absence of the canonical TATA and CAAT boxes in the 5'-flanking region, which contains many potential regulatory sequences, such as the E-box, N-box, Sp1 element, GATA-1 element, TAATGARAT element, and B2 short interspersed element (SINE) as well as several direct and inverted repeat sequences. The Etdf locus was assigned to the proximal region of mouse chromosome 7 using fluorescence in situ hybridization and linkage mapping analyses. These results provide the molecular basis for studying the regulation, in vivo function, and evolution of Etdf.
Refined mapping of a quantitative trait locus on chromosome 1 responsible for mouse embryonic death.
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Magalie Vatin
Full Text Available Recurrent spontaneous abortion (RSA is defined as the loss of three or more consecutive pregnancies during the first trimester of embryonic intrauterine development. This kind of human infertility is frequent among the general population since it affects 1 to 5% of women. In half of the cases the etiology remains unelucidated. In the present study, we used interspecific recombinant congenic mouse strains (IRCS in the aim to identify genes responsible for embryonic lethality. Applying a cartographic approach using a genotype/phenotype association, we identified a minimal QTL region, of about 6 Mb on chromosome 1, responsible for a high rate of embryonic death (∼30%. Genetic analysis suggests that the observed phenotype is linked to uterine dysfunction. Transcriptomic analysis of the uterine tissue revealed a preferential deregulation of genes of this region compared to the rest of the genome. Some genes from the QTL region are associated with VEGF signaling, mTOR signaling and ubiquitine/proteasome-protein degradation pathways. This work may contribute to elucidate the molecular basis of a multifactorial and complex human disorder as RSA.
Molecular hierarchy in neurons differentiated from mouse ES cells containing a single human chromosome 21.
Wang, Chi Chiu; Kadota, Mitsutaka; Nishigaki, Ryuichi; Kazuki, Yasuhiro; Shirayoshi, Yasuaki; Rogers, Michael Scott; Gojobori, Takashi; Ikeo, Kazuho; Oshimura, Mitsuo
Defects in neurogenesis and neuronal differentiation in the fetal brain of Down syndrome (DS) patients lead to the apparent neuropathological abnormalities and contribute to the phenotypic characters of mental retardation, and premature development of Alzheimer's disease, those being the most common phenotype in DS. In order to understand the molecular mechanism underlying the cause of phenotypic abnormalities in the DS brain, we have utilized an in vitro model of TT2F mouse embryonic stem cells containing a single human chromosome 21 (hChr21) to study neuron development and neuronal differentiation by microarray containing 15K developmentally expressed cDNAs. Defective neuronal differentiation in the presence of extra hChr21 manifested primarily the post-transcriptional and translational modification, such as Mrpl10, SNAPC3, Srprb, SF3a60 in the early neuronal stem cell stage, and Mrps18a, Eef1g, and Ubce8 in the late differentiated stage. Hierarchical clustering patterned specific expression of hChr21 gene dosage effects on neuron outgrowth, migration, and differentiation, such as Syngr2, Dncic2, Eif3sf, and Peg3.
Comparison of the chromosomal radiosensitivity of blood lymphocytes and stem-cell spermatogonia in the rhesus monkey and the mouse
International Nuclear Information System (INIS)
Buul, P.P.W. van; Richardson, J.F.; Boer, P. de; Zwanenburg, S.
By experiments similar to those with the mouse we studied, in the rhesus monkey (Macaca mulatta), the induction by X-rays of reciprocal translocations in steam-cell spermatogonia and of dicentric chromosomes in blood lymphocytes. Human blood lymphocytes and rhesus monkey lymphocytes showed about equal sensitivity to dicentric induction. This equal radiosensitivity of somatic cells, however, provides no clue to the quantitative extrapolation to the human situation of the data obtained on translocation induction in stem-cell spermatogonia of the rhesus monkey. In our opinion, only direct observations on induced chromosomal aberrations in germ cells of higher primates and man can play a decisive role in estimating human genetic radiation risks arising from chromosomal aberrations. (orig./AJ)
Radiation-induced chromosome aberrations in bone marrow cells leading to acute myeloid leukemia in mouse
International Nuclear Information System (INIS)
Nobuhiko Ban; Tomoko Kusama
It is well known that radiation-induced acute myeloid leukemia (RI-AML) in mice is charaterized by deletion and/or rearrangement of chromosome 2. While chromosome 2 has been suspected to be a target of RI-AML, radiation-sensitive site of the chromosome might be implicated in the leukemogenesis. There were few cytogenetical studies, however, focusing on chromosomal rearrangements shortly after irradiation, and little was known about the frequency and pattern of chromosome 2 aberrations during the early period. In this study, metaphase samples were prepared from whole-body irradiated mice 24 hours after irradiation, most of the cells considered to be in the first mitotic stage. Distribution of chromosomal breakpoints on the metaphase samples were analyzed to study the relationship between chromosome aberrations and RI-AML. (author)
The neurological mouse mutations jittery and hesitant are allelic and map to the region of mouse chromosome 10 homologous to 19p13.3
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Kapfhamer, D.; Sufalko, D.; Warren, S. [Univ. of Michigan, Ann Arbor, MI (United States)] [and others
Jittery (ji) is a recessive mouse mutation on Chromosome 10 characterized by progressive ataxic gait, dystonic movements, spontaneus seizures, and death by dehydration/starvation before fertility. Recently, a viable neurological recessive mutation, hesitant, was discovered. It is characterized by hesitant, uncoordinated movements, exaggerated stepping of the hind limbs, and reduced fertility in males. In a complementation test and by genetic mapping we have shown here that hesitant and jittery are allelic. Using several large intersubspecific backcrosses and intercrosses we have genetically mapped ji near the marker Amh and microsatellite markers D10Mit7, D10Mit21, and D10Mit23. The linked region of mouse Chromosome 10 is homologous to human 19p13.3, to which several human ataxia loci have recently been mapped. By excluding genes that map to human 21q22.3 (Pfkl) and 12q23 (Nfyb), we conclude that jittery is not likely to be a genetic mouse model for human Unverricht-Lundborg progressive myoclonus epilepsy (EPM1) on 21q22.3 nor for spinocerebellar ataxia II (SCA2) on 12q22-q24. The closely linked markers presented here will facilitate positional cloning of the ji gene. 31 refs., 2 figs.
Chromosome painting analysis of radiation-induced aberrant cell clones in the mouse
International Nuclear Information System (INIS)
Spruill, M.D.; Nath, J.; Tucker, J.D.
In a study of the persistence of radiation-induced translocations over the life span of the mouse, we observed a number of clonal cells in peripheral blood lymphocytes. The presence of clones caused the mean frequency of aberrations at various time points to be elevated which interfered with biodosimetry. For this reason, we have corrected our data for the presence of clones. Mice were given an acute dose of 0, 1, 2, 3 or 4 Gy 137 Cs at 8 weeks of age. Aberrations were measured by painting chromosomes 2 and 8 and cells were examined for clones at 3 months and every 3 months thereafter until 21 months. Clones were identified by comparing the color photographic slides of all abnormal cells from each animal. Determination of clonality was made on the basis of similar breakpoint locations or the presence of other identifying characteristics such as unusual aberrations. To correct the frequency of translocations for the presence of clones, each clone, regardless of how many cells it contained, was counted only once. This reflects the original aberration frequency since each clone originated as only one cell. Among mice exposed to 4 Gy, the mean frequencies of aberrant cell clones ranged from 3-29% of the total number of metaphase cells scored with the highest frequency being 1 year post exposure. 32-70% of reciprocal and 19-92% of non-reciprocal translocations were clonal. A dose response relationship for clones was evident until 21 months when the unexposed animals exhibited a mean frequency of aberrant cell clones >10% of the total number of cells scored. Almost 75% of reciprocal and 95% of non-reciprocal translocations in these unexposed control animals were of clonal origin. Correction for clonal expansion greatly reduced the means and their standard errors at most time points where clonal expansion was prevalent. The biodosimetry was much improved suggesting that correction is beneficial in long-term studies
G/sub 2/ arrest in mouse zygotes after X-irradiation: reversion by caffeine and influence of chromosome abnormalities
Energy Technology Data Exchange (ETDEWEB)
Grinfeld, S.; Jacquet, P.
The effect of caffeine was studied on mouse zygotes blocked in the G/sub 2/ phase of the first cell cycle after X-irradiation. Caffeine (2 mM) effectively reversed the G/sub 2/ arrest when zygotes were incubated in its presence at the time when first mitosis normally takes place. This effect of caffeine was inhibited by cycloheximide (5 ..mu..g ml/sup -1/). In embryos escaping the G/sub 2/ arrest the frequencies of chromosome aberrations varied as a function of the time of irradiation, showing a clear relationship with the varying rates of lethality occurring from the morula stage. Blocked zygotes suffered major chromosome damage: however, this did not appear to be the only cause of the G/sub 2/ arrest. Triploid zygotes were preferentially blocked, suggesting that nuclei contain the target for this X-ray effect.
An intron capture strategy used to identify and map a lysyl oxidase-like gene on chromosome 9 in the mouse
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Wydner, K.S.; Passmore, H.C. [Rutgers Univ., Piscataway, NJ (United States); Kim, Houngho; Csiszar, K.; Boyd, C.D. [UMDNJ, New Brunswick, NJ (United States)
An intron capture strategy involving use of polymerase chain reaction was used to identify and map the mouse homologue of a human lysyl oxidase-like gene (LOXL). Oligonucleotides complementary to conserved domains within exons 4 and 5 of the human lysyl oxidase-like gene were used to amplify the corresponding segment from mouse genomic DNA. Sequencing of the resulting mouse DNA fragment of approximately 1 kb revealed that the exon sequences at the ends of the amplified fragment are highly homologous (90% nucleotide identity) to exons 4 and 5 of the human lysyl oxidase-like gene. An AluI restriction site polymorphism within intron 4 was used to map the mouse lysyl oxidase-like gene (Loxl) to mouse Chromosome 9 in a region that shares linkage conservation with human chromosome 15q24, to which the LOXL was recently mapped. 22 refs., 3 figs.
Damage of chromosomes in mouse bone marrow cells after combined treatment with gamma radiation and cyclophosphamide
International Nuclear Information System (INIS)
Rupova, Ivanka
Full text: Current approaches to successful management of malignancy include combined modalities of treatment with ionizing radiation and anticancer drugs. Together with tumor cells normal tissues and cells are also submitted to the damaging effect of these agents, creating thus a probability for development of secondary neoplastic processes. The aim of the present study was to investigate the rate of chromosome damage at different modalities of combined exposures to gamma irradiation and cyclophosphamide(CY) of mice. Chromosomal aberration frequency in metaphase bone marrow cells was used as a measure to evaluate the effect. Combination treatments with 3 Gy gamma irradiation and 20 mg/kg cyclophosphamide were given at different intervals - simultaneously or at 12 hr interval, in order to establish the conditions and factors influencing the rate of chromosome damage. The distribution of different types of chromosome aberrations, such as chromatid fragments, chromatid exchanges, chromosome fragments and chromosome exchanges was analyzed. The results showed a high synergistic effect at simultaneous treatment with both agents if assessed by the index of aberrations per cell (%). An attempt has been made to suggest a possible explanation of the effects at different combined treatments related to the type of induced chromosomal aberrations. (author)
Casein kinase 1 alpha regulates chromosome congression and separation during mouse oocyte meiotic maturation and early embryo development.
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Lu Wang
Full Text Available Casein kinase I alpha (CK1α is a member of serine/threonine protein kinase, generally present in all eukaryotes. In mammals, CK1α regulates the transition from interphase to metaphase in mitosis. However, little is known about its role in meiosis. Here we examined Ck1α mRNA and protein expression, as well as its subcellular localization in mouse oocytes from germinal vesicle to the late 1-cell stage. Our results showed that the expression level of CK1α was increased in metaphase. Immunostaining results showed that CK1α colocalized with condensed chromosomes during oocyte meiotic maturation and early embryo development. We used the loss-of-function approach by employing CK1α specific morpholino injection to block the function of CK1α. This functional blocking leads to failure of polar body 1 (PB1 extrusion, chromosome misalignment and MII plate incrassation. We further found that D4476, a specific and efficient CK1 inhibitor, decreased the rate of PB1 extrusion. Moreover, D4476 resulted in giant polar body extrusion, oocyte pro-MI arrest, chromosome congression failure and impairment of embryo developmental potential. In addition, we employed pyrvinium pamoate (PP, an allosteric activator of CK1α, to enhance CK1α activity in oocytes. Supplementation of PP induced oocyte meiotic maturation failure, severe congression abnormalities and misalignment of chromosomes. Taken together, our study for the first time demonstrates that CK1α is required for chromosome alignment and segregation during oocyte meiotic maturation and early embryo development.
Nicotine-induced Disturbances of Meiotic Maturation in Cultured Mouse Oocytes: Alterations of Spindle Integrity and Chromosome Alignment
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Zenzes Maria
Full Text Available Abstract We investigated whether nicotine exposure in vitro of mouse oocytes affects spindle and chromosome function during meiotic maturation (M-I and M-II. Oocytes in germinal vesicle (GV stage were cultured in nicotine for 8 h or for 16 h, to assess effects in M-I and in metaphase II (M-II. The latter culture setting used the three protocols: 8 h nicotine then 8 h medium (8N + 8M; 16 h nicotine (16N; 8 h medium then 8 h nicotine (8M + 8N. Non-toxic concentrations of nicotine at 1.0, 2.5, 5.0 and 10.0 mmol/L were used. Spindle-chromosome configurations were analyzed with wide-field optical sectioning microscopy. In 8 h cultures, nicotine exposure resulted in dose-related increased proportions of M-I oocytes with defective spindle-chromosome configurations. A dose-related delayed entry into anaphase I was also detected. In 16 h cultures, nicotine exposure for the first 8 h (8N + 8M, or for 16 h (16N, resulted in dose- and time-related increased proportions of oocytes arrested in M-I (10 mmol/L; 8 h: 53.2%, controls 9.6%; 16 h: 87.6%, controls 8.5%. Defects in M-I spindles and chromosomes caused M-I arrest leading to dose-related decreased proportions of oocytes that reached metaphase-II (10 mmol/L 8 h: 46.8%, controls 90.4%;16 h: 12.4%, controls 91.5%. A delayed anaphase-I affected the normal timing of M-II, leading to abnormal oocytes with dispersed chromosomes, or with double spindles and no polar body. Nicotine exposure during the second 8 h (8M + 8N resulted in dose-related, increased proportions of M-II oocytes with defective spindles and chromosomes (10 mmol/L: 42.9%, controls 2.0%. Nicotine has no adverse effects on GV break down, but induces spindle and chromosome defects compromising oocyte meiotic maturation and development.
The Charles River "hairless" rat mutation maps to chromosome 1: allelic with fuzzy and a likely orthologue of mouse frizzy.
Ahearn, K; Akkouris, G; Berry, P R; Chrissluis, R R; Crooks, I M; Dull, A K; Grable, S; Jeruzal, J; Lanza, J; Lavoie, C; Maloney, R A; Pitruzzello, M; Sharma, R; Stoklasek, T A; Tweeddale, J; King, T R
Recent evidence has indicated that the recessive mutation affecting hypotrichosis in the Charles River (CR) "hairless" rat does not involve the hairless gene (hr) on rat chromosome 15. To determine if this mutation might be allelic (or orthologous) with any other previously mapped hypotrichosis-generating mutation in mammals, we have produced a panel of backcross rats segregating for the CR hairless rat mutation as well as numerous other markers from throughout the rat genome. Analysis of this panel has located the CR hairless rat's hypotrichosis-generating mutation on chromosome 1, near Myl2, where only the fuzzy mutation in rat (fz) and the frizzy mutation in mouse (fr) have been previously localized. Intercrossing fz/fz and CR hairless rats produced hybrid offspring with abnormal hair, showing that these two rat mutations are allelic. We suggest that the CR hairless rat mutation and fuzzy be renamed frizzy-Charles River (fr(CR)) and frizzy-Harlan (fr(H)), respectively, to reflect their likely orthology with the mouse fr mutation.
X-linked gene expression and X-chromosome inactivation: marsupials, mouse, and man compared.
VandeBerg, J L; Robinson, E S; Samollow, P B; Johnston, P G
The existence of paternal X inactivation in Australian and American marsupial species suggests that this feature of X-chromosome dosage compensation is not a recent adaptation, but probably predates the evolutionary separation of the Australian and American marsupial lineages. Although it is theoretically possible that the marsupial system is one of random X inactivation with p greater than 0.99 and q less than 0.01 and dependent on parental source, no instance of random X inactivation (p = q or p not equal to q) has ever been verified in any tissue or cell type of any marsupial species. Therefore, we conclude that the most fundamental difference in X inactivation of marsupials and eutherians is whether the inactive X is the paternal one or is determined at random (with p = q in most but not all cases). The only other unequivocal difference between eutherians and marsupials is that both X chromosomes are active in mice and human oocytes, but not in kangaroo oocytes. Apparently, the inactive X is reactivated at a later meiotic stage or during early embryogenesis in kangaroos. X-chromosome inactivation takes place early in embryogenesis of eutherians and marsupials. Extraembryonic membranes of mice exhibit paternal X inactivation, whereas those of humans seem to exhibit random X inactivation with p greater than q (i.e., preferential paternal X inactivation). In general, extraembryonic membranes of marsupial exhibit paternal X inactivation, but the Gpd locus is active on both X chromosomes in at least some cells of kangaroo yolk sac. It is difficult to draw any general conclusion because of major differences in embryogeny of mice, humans, and marsupials, and uncertainties in interpreting the data from humans. Other differences between marsupials and eutherians in patterns of X-linked gene expression and X-chromosome inactivation seem to be quantitative rather than qualitative. Partial expression of some genes on the inactive X is characteristic of marsupials, with
Chromosomal analysis in mouse eggs fertilized in vitro with sperm exposed to ultraviolet light (UV) and methyl and ethyl methanesulfonate (MMS and EMS)
International Nuclear Information System (INIS)
Matsuda, Y.; Tobari, I.
Chromosome aberrations were analyzed at the first-cleavage metaphase of mouse eggs fertilized in vitro with sperm exposed to ultraviolet light (UV) as well as to methyl and ethyl methanesulfonate (MMS and EMS). The frequencies of chromosome aberrations markedly increased with dose of UV as well as with concentration of MMS and EMS. In the UV-irradiation group, the frequency of chromosome-type aberrations was much higher than that of chromatid-type aberrations. About 90% of chromosome aberrations observed in the eggs following MMS and EMS treatment to sperm were chromosome type in which the frequency of chromosome fragments was the highest. The effects of UV on the induction of chromosome aberrations were clearly potentiated by post-treatment incubation of fertilized eggs in the presence of Ara-C or caffeine, but the effects of MMS and EMS were not pronounced by post-treatment of Ara-C or caffeine. The results indicate a possibility that UV damage induced in mouse sperm DNA is reparable in the eggs during the period between the entry of sperm into the egg cytoplasm and the first-cleavage metaphase. 35 refs.; 5 figs.; 4 tabs
Mouse tetranectin: cDNA sequence, tissue-specific expression, and chromosomal mapping
DEFF Research Database (Denmark)
Ibaraki, K; Kozak, C A; Wewer, U M
regulation, mouse tetranectin cDNA was cloned from a 16-day-old mouse embryo library. Sequence analysis revealed a 992-bp cDNA with an open reading frame of 606 bp, which is identical in length to the human tetranectin cDNA. The deduced amino acid sequence showed high homology to the human cDNA with 76......(s) of tetranectin. The sequence analysis revealed a difference in both sequence and size of the noncoding regions between mouse and human cDNAs. Northern analysis of the various tissues from mouse, rat, and cow showed the major transcript(s) to be approximately 1 kb, which is similar in size to that observed...
X-ray-induced chromosome aberrations in the leucocytes of mouse and man
International Nuclear Information System (INIS)
Preston, R.J.; Brewen, J.G.
In earlier studies it was shown that the frequency of dicentrics induced by X-rays in human leucocytes was about twice that induced in mouse leucocytes. The frequencies of deletions were similar in both species. However, the mouse cultures were fixed at 60 h and the human cultures at 54 h. In both cases it was likely that some of the cells analysed were in their second post-treatment mitosis. Further studies were carried out using fixation times of 48 h for both mouse and human cultures (three different human donors were used). The same relationships held here, namely twice as many dicentrics in humans, and similar deletion frequencies in both. The aberration frequencies observed were corrected to take account of second-diversion cells by assuming that cells containing a dicentric without an accompanying fragment were in their second division. There were more such cells in mouse than in human cultures. Further to increase reliance on the conclusions, cultures were fixed at the earliest times that 300 cells per dose could be obtained - 36 h for the mouse, 42 h for the human. The frequencies of dicentrics were increased in both, and a relationship of about 2:1 for human to mouse was obtained. Deletion frequencies were similar in both. Since no dicentrics without fragments were obtained, it appeared that aberration frequencies in first-division cells only were being compared. (author)
Sex-chromosome heterochromatin variation in the wood mouse, Apodemus sylvaticus
Czech Academy of Sciences Publication Activity Database
Nová, P.; Reutter, B. A.; Rábová, Marie; Zima, Jan
Roč. 96, 1-4 (2002), s. 186-190 ISSN 0301-0171 R&D Projects: GA AV ČR KSK6005114 Keywords : sex-chromosome * Apodemus sylvaticus Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.114, year: 2002
Position on mouse chromosome 1 of a gene that controls resistance to Salmonella typhimurium.
Taylor, B A; O'Brien, A D
Ity is a gene which regulates the magnitude of Salmonella typhimurium growth in murine tissues and, hence, the innate salmonella resistance of mice. The results of a five-point backcross clearly showed that the correct gene order on chromosome 1 is fz-Idh-1-Ity-ln-Pep-3.
Differential response of biochemical parameters to EMS and MMS treatments and their dose effect relationship on chromosomes in induced diabetic mouse
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B.B.D. Khalandar
Conclusion: (1 Even though alkylating agents induce chromosomal aberrations in diabetic mice, MMS, a methylating agent is a more potent inducer of chromatid type of aberrations than EMS, an ethylating agent. (2 Diabetic mouse is more resistant than the non diabetic to alkylating agents and (3 the tested agents altered the analyzed biochemical parameters.
Enzymatic amplification of a Y chromosome repeat in a single blastomere allows identification of the sex of preimplantation mouse embryos
International Nuclear Information System (INIS)
Bradbury, M.W.; Isola, L.M.; Gordon, J.W.
The polymerase chain reaction (PCR) technique has been adapted to identify the sex of preimplantation mouse embryos rapidly. PCR was used to amplify a specific repeated DNA sequence on the Y chromosome from a single isolated blastomere in under 12 hr. The remainder of the biopsied embryo was then transferred to a pseudopregnant female and carried to term. Using this technique, 72% of embryos can be classed as potentially either male or female. Transfers of such embryos have produced pregnancies with 8/8 fetuses (100%) being of the predicted sex. Variations of the technique have demonstrated certain limitations to the present procedure as well as indicated possible strategies for improvement of the assay. The PCR technique may have wide application in the genetic analysis of preimplantation embryos
Mouse model of chromosome mosaicism reveals lineage-specific depletion of aneuploid cells and normal developmental potential.
Bolton, Helen; Graham, Sarah J L; Van der Aa, Niels; Kumar, Parveen; Theunis, Koen; Fernandez Gallardo, Elia; Voet, Thierry; Zernicka-Goetz, Magdalena
Most human pre-implantation embryos are mosaics of euploid and aneuploid cells. To determine the fate of aneuploid cells and the developmental potential of mosaic embryos, here we generate a mouse model of chromosome mosaicism. By treating embryos with a spindle assembly checkpoint inhibitor during the four- to eight-cell division, we efficiently generate aneuploid cells, resulting in embryo death during peri-implantation development. Live-embryo imaging and single-cell tracking in chimeric embryos, containing aneuploid and euploid cells, reveal that the fate of aneuploid cells depends on lineage: aneuploid cells in the fetal lineage are eliminated by apoptosis, whereas those in the placental lineage show severe proliferative defects. Overall, the proportion of aneuploid cells is progressively depleted from the blastocyst stage onwards. Finally, we show that mosaic embryos have full developmental potential, provided they contain sufficient euploid cells, a finding of significance for the assessment of embryo vitality in the clinic.
A new chromosomal race of the house mouse, Mus musculus domesticus, in the Vulcano Island-Aeolian Archipelago, Italy.
Solano, Emanuela; Castiglia, Riccardo; Corti, Marco
In this paper we describe a new Robertsonian (Rb) race of the house mouse from Vulcano (Aeolian archipelago) through the identification of the metacentric chromosomes. We analysed fifteen mice. All the specimens were found to have the same karyotype 2n=26. This karyotype is characterized by Rb(1.2), Rb(3.9), Rb(4.13), Rb(5.14), Rb(8.12), Rb(10.16) and Rb(15.17). The differences between the race of Vulcano and the races in a neighbour island (Lipari) consist in the presence of Rb(10.16) and Rb(15.17) in the former and Rb(6.16) and Rb(10.15) in the latter. We discuss the possible hypotheses regarding the origin between these two races including the possible occurrence of a whole arm reciprocal translocation (WART) on the Vulcano island.
A knock-in/knock-out mouse model of HSPB8-associated distal hereditary motor neuropathy and myopathy reveals toxic gain-of-function of mutant Hspb8.
Bouhy, Delphine; Juneja, Manisha; Katona, Istvan; Holmgren, Anne; Asselbergh, Bob; De Winter, Vicky; Hochepied, Tino; Goossens, Steven; Haigh, Jody J; Libert, Claude; Ceuterick-de Groote, Chantal; Irobi, Joy; Weis, Joachim; Timmerman, Vincent
Mutations in the small heat shock protein B8 gene (HSPB8/HSP22) have been associated with distal hereditary motor neuropathy, Charcot-Marie-Tooth disease, and recently distal myopathy. It is so far not clear how mutant HSPB8 induces the neuronal and muscular phenotypes and if a common pathogenesis lies behind these diseases. Growing evidence points towards a role of HSPB8 in chaperone-associated autophagy, which has been shown to be a determinant for the clearance of poly-glutamine aggregates in neurodegenerative diseases but also for the maintenance of skeletal muscle myofibrils. To test this hypothesis and better dissect the pathomechanism of mutant HSPB8, we generated a new transgenic mouse model leading to the expression of the mutant protein (knock-in lines) or the loss-of-function (functional knock-out lines) of the endogenous protein Hspb8. While the homozygous knock-in mice developed motor deficits associated with degeneration of peripheral nerves and severe muscle atrophy corroborating patient data, homozygous knock-out mice had locomotor performances equivalent to those of wild-type animals. The distal skeletal muscles of the post-symptomatic homozygous knock-in displayed Z-disk disorganisation, granulofilamentous material accumulation along with Hspb8, αB-crystallin (HSPB5/CRYAB), and desmin aggregates. The presence of the aggregates correlated with reduced markers of effective autophagy. The sciatic nerve of the homozygous knock-in mice was characterized by low autophagy potential in pre-symptomatic and Hspb8 aggregates in post-symptomatic animals. On the other hand, the sciatic nerve of the homozygous knock-out mice presented a normal morphology and their distal muscle displayed accumulation of abnormal mitochondria but intact myofiber and Z-line organisation. Our data, therefore, suggest that toxic gain-of-function of mutant Hspb8 aggregates is a major contributor to the peripheral neuropathy and the myopathy. In addition, mutant Hspb8 induces
Assessing multilocus introgression patterns: a case study on the mouse X chromosome in Central Europe
Czech Academy of Sciences Publication Activity Database
Macholán, Miloš; Baird, S. J. E.; Dufková, Petra; Munclinger, P.; Vošlajerová Bímová, Barbora; Piálek, Jaroslav
Roč. 65, č. 5 (2011), s. 1428-1446 ISSN 0014-3820 R&D Projects: GA ČR GA206/08/0640 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z60930519 Keywords : genetic conflict * hybrid zone movement * sex biased introgression * mice * X chromosome Subject RIV: EG - Zoology Impact factor: 5.146, year: 2011
Karyotypic variation between wood mouse species: banded chromosomes of Apodemus alpicola and A. microps
Czech Academy of Sciences Publication Activity Database
Reutter, B. A.; Nová, P.; Vogel, P.; Zima, Jan
Roč. 46, č. 4 (2001), s. 353-362 ISSN 0001-7051 R&D Projects: GA MŠk VS97102 Institutional research plan: CEZ:AV0Z6093917 Keywords : Apodemus * Sylvaemus * chromosomal banding Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 0.652, year: 2001 http://acta.zbs.bialowieza.pl/contents/? art =2001-046-4-0353
Mouse Chromosome 4 Is Associated with the Baseline and Allergic IgE Phenotypes
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Cynthia Kanagaratham
Full Text Available Regulation of IgE concentration in the blood is a complex trait, with high concentrations associated with parasitic infections as well as allergic diseases. A/J strain mice have significantly higher plasma concentrations of IgE, both at baseline and after ovalbumin antigen exposure, when compared to C57BL/6J strain mice. Our objective was to determine the genomic regions associated with this difference in phenotype. To achieve this, we used a panel of recombinant congenic strains (RCS derived from A/J and C57BL/6J strains. We measured IgE in the RCS panel at baseline and following allergen exposure. Using marker by marker analysis of the RCS genotype and phenotype data, we identified multiple regions associated with the IgE phenotype. A single region was identified to be associated with baseline IgE level, while multiple regions wereassociated with the phenotype after allergen exposure. The most significant region was found on Chromosome 4, from 81.46 to 86.17 Mbp. Chromosome 4 substitution strain mice had significantly higher concentration of IgE than their background parental strain mice, C57BL/6J. Our data presents multiple candidate regions associated with plasma IgE concentration at baseline and following allergen exposure, with the most significant one located on Chromosome 4.
Aurora kinase A is essential for correct chromosome segregation in mouse zygote
Czech Academy of Sciences Publication Activity Database
Kovaříková, V.; Burkus, J.; Rehák, P.; Brzáková, Adéla; Šolc, Petr; Baran, V.
Roč. 24, č. 3 (2016), s. 326-337 ISSN 0967-1994 R&D Projects: GA MŠk ED2.1.00/03.0124 Institutional support: RVO:67985904 Keywords : apoptosis * aurora A * MLN8237 * mouse zygote * spindle Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.053, year: 2016
The tobacco mouse and its relatives: a "tail" of coat colors, chromosomes, hybridization and speciation
Czech Academy of Sciences Publication Activity Database
Hauffe, H. C.; Panithanarak, T.; Dallas, J. F.; Piálek, Jaroslav; Gündüz, I.; Searle, J. B.
Roč. 105, 2-4 (2004), s. 395-405 ISSN 1424-8581 Institutional research plan: CEZ:AV0Z6093917 Keywords : mouse * mitochondrial DNA * hybrid zones Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 1.341, year: 2004
Gtl2lacZ, an insertional mutation on mouse chromosome 12 with parental origin-dependent phenotype.
Schuster-Gossler, K; Simon-Chazottes, D; Guenet, J L; Zachgo, J; Gossler, A
We have produced a transgenic mouse line, Gtl2lacZ (Gene trap locus 2), that carries an insertional mutation with a dominant modified pattern of inheritance:heterozygous Gtl2lacZ mice that inherited the transgene from the father show a proportionate dwarfism phenotype, whereas the penetrance and expressivity of the phenotype is strongly reduced in Gtl2lacZ mice that inherited the transgene from the mother. On a mixed genetic background this pattern of inheritance was reversible upon transmission of the transgene through the germ line of the opposite sex. On a predominantly 129/Sv genetic background, however, transgene passage through the female germ line modified the transgene effect, such that the penetrance of the mutation was drastically reduced and the phenotype was no longer obvious after subsequent male germ line transmission. Expression of the transgene, however, was neither affected by genetic background nor by parental legacy. Gtl2lacZ maps to mouse Chromosome 12 in a region that displays imprinting effects associated with maternal and paternal disomy. Our results suggest that the transgene insertion in Gtl2lacZ mice affects an endogenous gene(s) required for fetal and postnatal growth and that this gene(s) is predominantly paternally expressed.
International Nuclear Information System (INIS)
Heermann, Dieter W.
Mounting evidence is compiling linking the physical organizational structure of chromosomes and the nuclear structure to biological function. At the base of the physical organizational structure of both is the concept of loop formation. This implies that physical proximity within chromosomes is provided for otherwise distal genomic regions and thus hierarchically organizing the chromosomes. Together with entropy many experimental observations can be explained with these two concepts. Among the observations that can be explained are the measured physical extent of the chromosomes, their shape, mechanical behavior, the segregation into territories (chromosomal and territories within chromosomes), the results from chromosome conformation capture experiments, as well as linking gene expression to structural organization.
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Heermann, Dieter W., E-mail: email@example.com
Mounting evidence is compiling linking the physical organizational structure of chromosomes and the nuclear structure to biological function. At the base of the physical organizational structure of both is the concept of loop formation. This implies that physical proximity within chromosomes is provided for otherwise distal genomic regions and thus hierarchically organizing the chromosomes. Together with entropy many experimental observations can be explained with these two concepts. Among the observations that can be explained are the measured physical extent of the chromosomes, their shape, mechanical behavior, the segregation into territories (chromosomal and territories within chromosomes), the results from chromosome conformation capture experiments, as well as linking gene expression to structural organization.
Fine genetic map of mouse chromosome 10 around the polycystic kidney disease gene, jcpk, and ankyrin 3
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Bryda, E.C.; Ling, H.; Rathbun, D.E. [New York State Department of Health, Albany, NY (United States)] [and others
A chlorambucil (CHL)-induced mutation of the jcpk (juvenile congenital polycystic kidney disease) gene causes a severe early onset polycystic kidney disease. In an intercross involving Mus musculus castaneus, jcpk was precisely mapped 0.2 cM distal to D10Mit115 and 0.8 cM proximal to D10Mit173. In addition, five genes, Cdc2a, Col6al, Col6a2, Bcr, and Ank3 were mapped in both this jcpk intercross and a (BALB/c X CAST/Ei)F{sub 1} x BALB/c backcross. All five genes were eliminated as possible candidates for jcpk based on the mapping data. The jcpk intercross allowed the orientation of the Ank3 gene relative to the centromere to be determined. D10Mit115, D10Mit173, D10Mit199, and D10Mit200 were separated genetically in this cross. The order and genetic distances of all markers and gene loci mapped in the jcpk intercross were consistent with those derived from the BALB/c backcross, indicating that the CHL-induced lesion has not generated any gross chromosomal abnormalities detectable in these studies. 39 refs., 3 figs.
Segmental trisomy of chromosome 17: a mouse model of human aneuploidy syndromes
Czech Academy of Sciences Publication Activity Database
Vacík, Tomáš; Ort, Michael; Gregorová, Soňa; Strnad, P.; Conte, N.; Bradley, A.; Blatný, Radek; Bureš, Jan; Forejt, Jiří
Roč. 102, č. 12 (2005), s. 4500-4505 ISSN 0027-8424 R&D Projects: GA ČR(CZ) GA309/03/0715 Grant - others:Howard Hughes Medical Institute(US) 55000306 Institutional research plan: CEZ:AV0Z5011922; CEZ:AV0Z50110509 Keywords : dosage-sensitive genes * Down's syndrome * mouse segmental trisomy Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 10.231, year: 2005
Direct physical contact between intercalated cells in the distal convoluted tubule and the afferent arteriole in mouse kidneys.
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Hao Ren
Full Text Available Recent physiological studies in the kidney proposed the existence of a secondary feedback mechanism termed 'crosstalk' localized after the macula densa. This newly discovered crosstalk contact between the nephron tubule and its own afferent arteriole may potentially revolutionize our understanding of renal vascular resistance and electrolyte regulation. However, the nature of such a crosstalk mechanism is still debated due to a lack of direct and comprehensive morphological evidence. Its exact location along the nephron, its prevalence among the different types of nephrons, and the type of cells involved are yet unknown. To address these issues, computer assisted 3-dimensional nephron tracing was applied in combination with direct immunohistochemistry on plastic sections and electron microscopy. 'Random' contacts in the cortex were identified by the tracing and excluded. We investigated a total of 168 nephrons from all cortical regions. The results demonstrated that the crosstalk contact existed, and that it was only present in certain nephrons (90% of the short-looped and 75% of the long-looped nephrons. The crosstalk contacts always occurred at a specific position--the last 10% of the distal convoluted tubule. Importantly, we demonstrated, for the first time, that the cells found in the tubule wall at the contact site were always type nonA-nonB intercalated cells. In conclusion, the present work confirmed the existence of a post macula densa physical crosstalk contact.
Direct physical contact between intercalated cells in the distal convoluted tubule and the afferent arteriole in mouse kidneys.
Ren, Hao; Liu, Ning-Yu; Andreasen, Arne; Thomsen, Jesper S; Cao, Liu; Christensen, Erik I; Zhai, Xiao-Yue
Recent physiological studies in the kidney proposed the existence of a secondary feedback mechanism termed 'crosstalk' localized after the macula densa. This newly discovered crosstalk contact between the nephron tubule and its own afferent arteriole may potentially revolutionize our understanding of renal vascular resistance and electrolyte regulation. However, the nature of such a crosstalk mechanism is still debated due to a lack of direct and comprehensive morphological evidence. Its exact location along the nephron, its prevalence among the different types of nephrons, and the type of cells involved are yet unknown. To address these issues, computer assisted 3-dimensional nephron tracing was applied in combination with direct immunohistochemistry on plastic sections and electron microscopy. 'Random' contacts in the cortex were identified by the tracing and excluded. We investigated a total of 168 nephrons from all cortical regions. The results demonstrated that the crosstalk contact existed, and that it was only present in certain nephrons (90% of the short-looped and 75% of the long-looped nephrons). The crosstalk contacts always occurred at a specific position--the last 10% of the distal convoluted tubule. Importantly, we demonstrated, for the first time, that the cells found in the tubule wall at the contact site were always type nonA-nonB intercalated cells. In conclusion, the present work confirmed the existence of a post macula densa physical crosstalk contact.
The Phosphatase Dusp7 Drives Meiotic Resumption and Chromosome Alignment in Mouse Oocytes
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Thomas Tischer
Full Text Available Mammalian oocytes are stored in the ovary, where they are arrested in prophase for prolonged periods. The mechanisms that abrogate the prophase arrest in mammalian oocytes and reinitiate meiosis are not well understood. Here, we identify and characterize an essential pathway for the resumption of meiosis that relies on the protein phosphatase DUSP7. DUSP7-depleted oocytes either fail to resume meiosis or resume meiosis with a significant delay. In the absence of DUSP7, Cdk1/CycB activity drops below the critical level required to reinitiate meiosis, precluding or delaying nuclear envelope breakdown. Our data suggest that DUSP7 drives meiotic resumption by dephosphorylating and thereby inactivating cPKC isoforms. In addition to controlling meiotic resumption, DUSP7 has a second function in chromosome segregation: DUSP7-depleted oocytes that enter meiosis show severe chromosome alignment defects and progress into anaphase prematurely. Altogether, these findings establish the phosphatase DUSP7 as an essential regulator of multiple steps in oocyte meiosis.
Detailed ordering of markers localizing to the Xq26-Xqter region of the human X chromosome by the use of an interspecific Mus spretus mouse cross
International Nuclear Information System (INIS)
Avner, P.; Amar, L.; Arnaud, D.; Hanauer, A.; Cambrou, J.
Five probes localizing to the Xq26-Xqter region of the human X chromosome have been genetically mapped on the mouse X chromosome using an interspecific cross involving Mus spretus to a contiguous region lying proximally to the Tabby (Ta) locus. Pedigree and recombinational analysis establish the marker order as being Hprt-FIX-c11-G6PD-St14-1. The size of this contiguous region is such that the X-linked muscular dystrophy (mdx) mouse mutation probably maps within this segment. This in turn suggests that it is highly improbable that the mouse mdx locus represents a model for Duchenne muscular dystrophy (DMD). It is, however, compatible with the idea that this mutation may correspond in man to Emery Dreifuss muscular dystrophy. The high frequency of restriction fragment length polymorphisms found in this interspecific system for all the human cross-reacting probes examined up until now, using only a limited number of restriction enzymes, suggests that the Mus spretus mapping system may be of great potential value for establishing the linkage relationships existing in man when conserved chromosomal regions are concerned and human/mouse cross-reacting probes are available or can be obtained
Dimachkie, Mazen M.; Barohn, Richard J.
Over a century ago, Gowers described two young patients in whom distal muscles weakness involved the hand, foot, sternocleidomastoid, and facial muscles in the other case the shoulder and distal leg musculature. Soon after, , similar distal myopathy cases were reported whereby the absence of sensory symptoms and of pathologic changes in the peripheral nerves and spinal cord at postmortem examination allowed differentiation from Charcot-Marie-Tooth disease. In 1951, Welander described autosomal dominant (AD) distal arm myopathy in a large Scandanavian cohort. Since then the number of well-characterized distal myopathies has continued to grow such that the distal myopathies have formed a clinically and genetically heterogeneous group of disorders. Affected kindred commonly manifest weakness that is limited to foot and toe muscles even in advanced stages of the disease, with variable mild proximal leg, distal arm, neck and laryngeal muscle involvement in selected individuals. An interesting consequence of the molecular characterization of the distal myopathies has been the recognition that mutation in a single gene can lead to more than one clinical disorder. For example, Myoshi myopathy (MM) and limb girdle muscular dystrophy (LGMD) type 2B are allelic disorders due to defects in the gene that encodes dysferlin. The six well described distal myopathy syndromes are shown in Table 1. Table 2 lists advances in our understanding of the myofibrillar myopathy group and Table 3 includes more recently delineated and less common distal myopathies. In the same manner, the first section of this review pertains to the more traditional six distal myopathies followed by discussion of the myofibrillar myopathies. In the third section, we review other clinically and genetically distinctive distal myopathy syndromes usually based upon single or smaller family cohorts. The fourth section considers other neuromuscular disorders that are important to recognize as they display prominent
High-resolution linkage map of mouse chromosome 13 in the vicinity of the host resistance locus Lgn1
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Beckers, M.C.; Ernst, E.; Diez, E. [McGill Univ., Quebec (Canada)] [and others
Natural resistance of inbred mouse strains to infection with Legionella pneumophila is controlled by the expression of a single dominant gene on chromosome 13, designated Lgn1. The genetic difference at Lgn1 is phenotypically expressed as the presence or absence of intracellular replication of L. pneumophila in host macrophages. In our effort to identify the Lgn1 gene by positional cloning, we have generated a high-resolution linkage map of the Lgn1 chromosomal region. For this, we have carried out extensive segregation analysis in a total of 1270 (A/J x C57BL/6J) X A/J informative backcross mice segregating the resistance allele of C57BL/6J and the susceptibility allele of A/J. Additional segregation analyses were carried out in three preexisting panels of C57BL/6J X Mus spretus interspecific backcross mice. A total of 39 DNA markers were mapped within an interval of approximately 30 cM overlapping the Lgn1 region. Combined pedigree analyses for the 5.4-cM segment overlapping Lgn1 indicated the locus order and the interlocus distances (in cM): D13Mit128-(1.4)-D13Mit194-(0.1)-D13Mit147-(0.9)-Dl3Mit36-(0.9)-D13Mit146-(0.2)-Lgn1/D 13Mit37-(1.0)-D13Mit70. Additional genetic linkage studies of markers not informative in the A/J X C57BL/6J cross positioned D13Mit30, -72, -195, and -203, D13Gor4, D13Hun35, and Mtap5 in the immediate vicinity of the Lgn1 locus. The marker density and resolution of this genetic linkage map should allow the construction of a physical map of the region and the isolation of YAC clones overlapping the gene. 60 refs., 2 figs., 2 tabs.
Hypoxia inducible factor 3α plays a critical role in alveolarization and distal epithelial cell differentiation during mouse lung development.
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Yadi Huang
Full Text Available Lung development occurs under relative hypoxia and the most important oxygen-sensitive response pathway is driven by Hypoxia Inducible Factors (HIF. HIFs are heterodimeric transcription factors of an oxygen-sensitive subunit, HIFα, and a constitutively expressed subunit, HIF1β. HIF1α and HIF2α, encoded by two separate genes, contribute to the activation of hypoxia inducible genes. A third HIFα gene, HIF3α, is subject to alternative promoter usage and splicing, leading to three major isoforms, HIF3α, NEPAS and IPAS. HIF3α gene products add to the complexity of the hypoxia response as they function as dominant negative inhibitors (IPAS or weak transcriptional activators (HIF3α/NEPAS. Previously, we and others have shown the importance of the Hif1α and Hif2α factors in lung development, and here we investigated the role of Hif3α during pulmonary development. Therefore, HIF3α was conditionally expressed in airway epithelial cells during gestation and although HIF3α transgenic mice were born alive and appeared normal, their lungs showed clear abnormalities, including a post-pseudoglandular branching defect and a decreased number of alveoli. The HIF3α expressing lungs displayed reduced numbers of Clara cells, alveolar epithelial type I and type II cells. As a result of HIF3α expression, the level of Hif2α was reduced, but that of Hif1α was not affected. Two regulatory genes, Rarβ, involved in alveologenesis, and Foxp2, a transcriptional repressor of the Clara cell specific Ccsp gene, were significantly upregulated in the HIF3α expressing lungs. In addition, aberrant basal cells were observed distally as determined by the expression of Sox2 and p63. We show that Hif3α binds a conserved HRE site in the Sox2 promoter and weakly transactivated a reporter construct containing the Sox2 promoter region. Moreover, Hif3α affected the expression of genes not typically involved in the hypoxia response, providing evidence for a novel
The gene for the alpha 1 subunit of the skeletal muscle dihydropyridine-sensitive calcium channel (Cchl1a3) maps to mouse chromosome 1.
Chin, H; Krall, M; Kim, H L; Kozak, C A; Mock, B
Cchl1a3 encodes the dihydropyridine-sensitive calcium channel alpha 1 subunit isoform predominantly expressed in skeletal muscle. mdg (muscular dysgenesis) has previously been implicated as a mutant allele of this gene. Hybridization of a rat brain cDNA probe for Cchl1a3 to Southern blots of DNAs from a panel of Chinese hamster x mouse somatic cell hybrids suggested that this gene maps to mouse Chromosome 1. Analysis of the progeny of an inbred strain cross-positioned Cchl1a3 1.3 cM proximal to the Pep-3 locus on Chr 1.
Initiation of epigenetic reprogramming of the X chromosome in somatic nuclei transplanted to a mouse oocyte.
Bao, Siqin; Miyoshi, Naoki; Okamoto, Ikuhiro; Jenuwein, Thomas; Heard, Edith; Azim Surani, M
The active and inactive X chromosomes have distinct epigenetic marks in somatic nuclei, which undergo reprogramming after transplantation into oocytes. We show that, despite the disappearance of Xist RNA coating in 30 min, the epigenetic memory of the inactive X persists with the precocious appearance of histone H3 trimethylation of lysine 27 (H3-3meK27), without the expected colocalization with Eed/Ezh2. Subsequently, Xist re-appears on the original inactive X, and the silent Xist on the active X undergoes re-activation, resulting in unusual biallelic Xist RNA domains. Despite this abnormal Xist expression pattern, colocalization of H3-3meK27 and Eed is thereafter confined to a single Xist domain, which is presumably on the original inactive X. These epigenetic events differ markedly from the kinetics of preferential paternal X inactivation in normal embryos. All the epigenetic marks on the X are apparently erased in the epiblast, suggesting that the oocyte and epiblast may have distinct properties for stepwise programming of the genome.
Delayed formation of chromosome aberrations in mouse pachytebne spermatocytes treated with triethylenemelamine (TEM)
International Nuclear Information System (INIS)
Generoso, W.M.; Krishna, M.; Sotomayor, R.E.; Cacheiro, N.L.A.
Induction of chromosome aberrations in pachytene spermatocytes of mice by 2 mg/kg TEM was compared with induction by 400 R x rays. These doses induced comparably high dominant lethal effects in pachytene spermatocytes of mice. Cytological analysis at diakinesis-metaphase I stage showed that whereas 76.4% of the cells treated with x rays at pachytene stage had aberrations, the frequencies observed in two TEM experiments were only 0.8 and 2.2%. On the other hand, 5% of the progeny from TEM-treated pachytene spermatocytes were found to be translocation heterozygotes. This is the first report on the recovery of heritable translocations from treated spermatocytes of mice. The aberration frequencies observed for TEM in diakinesis-metaphase I were much too low to account for all the lethal mutations and heritable translocations. Thus, the formation of the bulk of aberrations induced by TEM in pachytene spermatocytes was delayed--a marked contrast to the more immediate formation of x-ray-induced aberrations. It is postulated that the formation of the bulk of TEM-induced aberrations in pachytene spermatocytes and in certain postmeiotic stages occurs sometime during spermiogenesis, and not through the operation of postfertilization pronuclear DNA synthesis
Localization of the homolog of a mouse craniofacial mutant to human chromosome 18q11 and evaluation of linkage to human CLP and CPO
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Griffith, A.J.; Burgess, D.L.; Kohrman, D.C.; Yu, J. [Univ. of Michigan, Ann Arbor, MI (United States)] [and others
The transgene-induced mutation 9257 and the spontaneous mutation twirler cause craniofacial and inner ear malformations and are located on mouse chromosome 18 near the ataxia locus ax. To map the human homolog of 9257, a probe from the transgene insertion site was used to screen a human genomic library. Analysis of a cross-hybridizing human clone identified a 3-kb conserved sequence block that does not appear to contain protein coding sequence. Analysis of somatic cell hybrid panels assigned the human locus to 18q11. The polymorphic microsatellite markers D18S1001 and D18S1002 were isolated from the human locus and mapped by linkage analysis using the CEPH pedigrees. The 9257 locus maps close to the centromeres of human chromosome 18q and mouse chromosome 18 at the proximal end of a conserved linkage group. To evaluate the role of this locus in human craniofacial disorders, linkage to D18S1002 was tested in 11 families with autosomal dominant nonsyndromic cleft lip and palate and 3 families with autosomal dominant cleft palate only. Obligatory recombinants were observed in 8 of the families, and negative lod scores from the other families indicated that these disorders are not linked to the chromosome 18 loci. 23 refs., 4 figs., 2 tabs.
Definition of the locus responsible for systemic carnitine deficiency within a 1.6-cM region of mouse chromosome 11 by detailed linkage analysis
Energy Technology Data Exchange (ETDEWEB)
Okita, Kohei; Tokino, Takashi; Nishimori, Hiroyuki [Univ. of Tokyo (Japan)] [and others
Carnitine is an essential cofactor for oxidation of mitochondrial fatty acids. Carnitine deficiency results in failure of energy production by mitochondria and leads to metabolic encephalopathy, lipid-storage myopathy, and cardiomyopathy. The juvenile visceral steatosis (JVS) mouse, an animal model of systemic carnitine deficiency, inherits the JVS phenotype in autosomal recessive fashion, through a mutant allele mapped to mouse chromosome 11. As a step toward identifying the gene responsible for JVS by positional cloning, we attempted to refine the jvs locus in the mouse by detailed linkage analysis with 13 microsatellite markers, using 190 backcross progeny. Among the 13 loci tested, 5 (defined by markers D11Mit24, D11Mit111,D11Nds9, D11Mit86, and D11Mit23) showed no recombination, with a maximum lod score of 52.38. Our results implied that the jvs gene can be sought on mouse chromosome 11 within a genetic distance no greater than about 1.6 cM. 21 refs., 2 figs.
An X-linked Myh11-CreERT2 mouse line resulting from Y to X chromosome-translocation of the Cre allele.
Liao, Mingmei; Zhou, Junmei; Wang, Fen; Ali, Yasmin H; Chan, Kelvin L; Zou, Fei; Offermanns, Stefan; Jiang, Zhisheng; Jiang, Zhihua
The Myh11-CreER T2 mouse line (Cre + ) has gained increasing application because of its high lineage specificity relative to other Cre drivers targeting smooth muscle cells (SMCs). This Cre allele, however, was initially inserted into the Y chromosome (X/Y Cre+ ), which excluded its application in female mice. Our group established a Cre + colony from male ancestors. Surprisingly, genotype screening identified female carriers that stably transmitted the Cre allele to the following generations. Crossbreeding experiments revealed a pattern of X-linked inheritance for the transgene (k > 1000), indicating that these female carries acquired the Cre allele through a mechanism of Y to X chromosome translocation. Further characterization demonstrated that in hemizygous X/X Cre+ mice Cre activity was restricted to a subset arterial SMCs, with Cre expression in arteries decreased by 50% compared to X/Y Cre+ mice. This mosaicism, however, diminished in homozygous X Cre+ /X Cre+ mice. In a model of aortic aneurysm induced by a SMC-specific Tgfbr1 deletion, the homozygous X Cre+ /X Cre+ Cre driver unmasked the aortic phenotype that is otherwise subclinical when driven by the hemizygous X/X Cre+ Cre line. In conclusion, the Cre allele carried by this female mouse line is located on the X chromosome and subjected to X-inactivation. The homozygous X Cre+ /X Cre+ mice produce uniform Cre activity in arterial SMCs. © 2017 Wiley Periodicals, Inc.
Association of a Chromosomal Rearrangement Event with Mouse Posterior Polymorphous Corneal Dystrophy and Alterations in Csrp2bp, Dzank1, and Ovol2 Gene Expression.
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Anna L Shen
Full Text Available We have previously described a mouse model of human posterior polymorphous corneal dystrophy (PPCD and localized the causative mutation to a 6.2 Mbp region of chromosome 2, termed Ppcd1. We now show that the gene rearrangement linked to mouse Ppcd1 is a 3.9 Mbp chromosomal inversion flanked by 81 Kbp and 542 bp deletions. This recombination event leads to deletion of Csrp2bp Exons 8 through 11, Dzank1 Exons 20 and 21, and the pseudogene Znf133. In addition, we identified translocation of novel downstream sequences to positions adjacent to Csrp2bp Exon 7 and Dzank1 Exon 20. Twelve novel fusion transcripts involving Csrp2bp or Dzank1 linked to downstream sequences have been identified. Eight are expressed at detectable levels in PPCD1 but not wildtype eyes. Upregulation of two Csrp2bp fusion transcripts, as well as upregulation of the adjacent gene, Ovol2, was observed. Absence of the PPCD1 phenotype in animals haploinsufficient for Csrp2bp or both Csrp2bp and Dzank1 rules out haploinsufficiency of these genes as a cause of mouse PPCD1. Complementation experiments confirm that PPCD1 embryonic lethality is due to disruption of Csrp2bp expression. The ocular expression pattern of Csrp2bp is consistent with a role for this protein in corneal development and pathogenesis of PPCD1.
SMC5/6 is required for the formation of segregation-competent bivalent chromosomes during meiosis I in mouse oocytes.
Hwang, Grace; Sun, Fengyun; O'Brien, Marilyn; Eppig, John J; Handel, Mary Ann; Jordan, Philip W
SMC complexes include three major classes: cohesin, condensin and SMC5/6. However, the localization pattern and genetic requirements for the SMC5/6 complex during mammalian oogenesis have not previously been examined. In mouse oocytes, the SMC5/6 complex is enriched at the pericentromeric heterochromatin, and also localizes along chromosome arms during meiosis. The infertility phenotypes of females with a Zp3-Cre -driven conditional knockout (cKO) of Smc5 demonstrated that maternally expressed SMC5 protein is essential for early embryogenesis. Interestingly, protein levels of SMC5/6 complex components in oocytes decline as wild-type females age. When SMC5/6 complexes were completely absent in oocytes during meiotic resumption, homologous chromosomes failed to segregate accurately during meiosis I. Despite what appears to be an inability to resolve concatenation between chromosomes during meiosis, localization of topoisomerase IIα to bivalents was not affected; however, localization of condensin along the chromosome axes was perturbed. Taken together, these data demonstrate that the SMC5/6 complex is essential for the formation of segregation-competent bivalents during meiosis I, and findings suggest that age-dependent depletion of the SMC5/6 complex in oocytes could contribute to increased incidence of oocyte aneuploidy and spontaneous abortion in aging females. © 2017. Published by The Company of Biologists Ltd.
Analysis of structural and numerical chromosomal aberrations at the first and second mitosis after X irradiation of two-cell mouse embryos
International Nuclear Information System (INIS)
Weissenborn, U.; Streffer, C.
Two-cell mouse embryos were X-irradiated in the late G2 phase in vivo. The first and second postradiation mitoses were analyzed for chromosomal anomalies. The majority of structural aberrations visible at the first mitosis after irradiation were chromatid breaks and chromatid gaps; only a few interchanges and dicentrics were observed. The aberration frequency resulted in a dose-effect relationship which was well described by a linear model. At the second mitosis 29% of the structural aberrations of the first mitosis were counted; the aberration quality changed only slightly. It is discussed whether these aberrations are to be considered new, derived, or unchanged transmitted aberrations. Contrary to the results obtained after irradiation of one-cell embryos, little chromosome loss was induced by radiation in two-cell embryos
Auditory function in the Tc1 mouse model of down syndrome suggests a limited region of human chromosome 21 involved in otitis media.
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Stephanie Kuhn
Full Text Available Down syndrome is one of the most common congenital disorders leading to a wide range of health problems in humans, including frequent otitis media. The Tc1 mouse carries a significant part of human chromosome 21 (Hsa21 in addition to the full set of mouse chromosomes and shares many phenotypes observed in humans affected by Down syndrome with trisomy of chromosome 21. However, it is unknown whether Tc1 mice exhibit a hearing phenotype and might thus represent a good model for understanding the hearing loss that is common in Down syndrome. In this study we carried out a structural and functional assessment of hearing in Tc1 mice. Auditory brainstem response (ABR measurements in Tc1 mice showed normal thresholds compared to littermate controls and ABR waveform latencies and amplitudes were equivalent to controls. The gross anatomy of the middle and inner ears was also similar between Tc1 and control mice. The physiological properties of cochlear sensory receptors (inner and outer hair cells: IHCs and OHCs were investigated using single-cell patch clamp recordings from the acutely dissected cochleae. Adult Tc1 IHCs exhibited normal resting membrane potentials and expressed all K(+ currents characteristic of control hair cells. However, the size of the large conductance (BK Ca(2+ activated K(+ current (I(K,f, which enables rapid voltage responses essential for accurate sound encoding, was increased in Tc1 IHCs. All physiological properties investigated in OHCs were indistinguishable between the two genotypes. The normal functional hearing and the gross structural anatomy of the middle and inner ears in the Tc1 mouse contrast to that observed in the Ts65Dn model of Down syndrome which shows otitis media. Genes that are trisomic in Ts65Dn but disomic in Tc1 may predispose to otitis media when an additional copy is active.
Repair of exogenous DNA double-strand breaks promotes chromosome synapsis in SPO11-mutant mouse meiocytes, and is altered in the absence of HORMAD1.
Carofiglio, Fabrizia; Sleddens-Linkels, Esther; Wassenaar, Evelyne; Inagaki, Akiko; van Cappellen, Wiggert A; Grootegoed, J Anton; Toth, Attila; Baarends, Willy M
Repair of SPO11-dependent DNA double-strand breaks (DSBs) via homologous recombination (HR) is essential for stable homologous chromosome pairing and synapsis during meiotic prophase. Here, we induced radiation-induced DSBs to study meiotic recombination and homologous chromosome pairing in mouse meiocytes in the absence of SPO11 activity (Spo11 YF/YF model), and in the absence of both SPO11 and HORMAD1 (Spo11/Hormad1 dko). Within 30 min after 5 Gy irradiation of Spo11 YF/YF mice, 140-160 DSB repair foci were detected, which specifically localized to the synaptonemal complex axes. Repair of radiation-induced DSBs was incomplete in Spo11 YF/YF compared to Spo11 +/YF meiocytes. Still, repair of exogenous DSBs promoted partial recovery of chromosome pairing and synapsis in Spo11 YF/YF meiocytes. This indicates that at least part of the exogenous DSBs can be processed in an interhomolog recombination repair pathway. Interestingly, in a seperate experiment, using 3 Gy of irradiation, we observed that Spo11/Hormad1 dko spermatocytes contained fewer remaining DSB repair foci at 48 h after irradiation compared to irradiated Spo11 knockout spermatocytes. Together, these results show that recruitment of exogenous DSBs to the synaptonemal complex, in conjunction with repair of exogenous DSBs via the homologous chromosome, contributes to homology recognition. In addition, the data suggest a role for HORMAD1 in DNA repair pathway choice in mouse meiocytes. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.
Mouse TRIP13/PCH2 Is Required for Recombination and Normal Higher-Order Chromosome Structure during Meiosis
Roig, I.; Dowdle, J.A.; Toth, A.; de Rooij, D.G.; Jasin, M.; Keeney, S.
Accurate chromosome segregation during meiosis requires that homologous chromosomes pair and become physically connected so that they can orient properly on the meiosis I spindle. These connections are formed by homologous recombination closely integrated with the development of meiosis-specific,
The relationship between cell killing, chromosome aberrations, spindle defects, and mitotic delay in mouse lymphoma cells of differential sensitivity to X-rays
International Nuclear Information System (INIS)
Scott, D.; Zampetti-Bosseler, F.
A study has been made of the effects of x radiation on an ultrasensitive subline of L5178Y mouse lymphoma cells. It has been shown that at survival levels above about 20 per cent, chromosome structural aberrations which lead to bridges and fragments at anaphase are about four times more frequent than spindle defects. The results demonstrated the higher frequency of structural aberrations and spindle defects, and the greater mitotic delay in the X-ray-sensitive than in the X-ray-resistant cell line. A model is proposed which causally relates these end-points to cell killing and DNA repair. (author)
Czech Academy of Sciences Publication Activity Database
Forejt, Jiří; Trachtulec, Zdeněk
Roč. 11, č. 11 (2000), s. 956-957 ISSN 0938-8990 R&D Projects: GA ČR GV204/98/K015; GA ČR GA204/98/P131; GA AV ČR IAA5052709 Institutional research plan: CEZ:AV0Z5052915 Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.137, year: 2000
cDNA cloning and characterization of the human THRAP2 gene which maps to chromosome 12q24, and its mouse ortholog Thrap2.
Musante, Luciana; Bartsch, Oliver; Ropers, Hans-Hilger; Kalscheuer, Vera M
Characterization of a balanced t(2;12)(q37;q24) translocation in a patient with suspicion of Noonan syndrome revealed that the chromosome 12 breakpoint lies in the vicinity of a novel human gene, thyroid hormone receptor-associated protein 2 (THRAP2). We therefore characterized this gene and its mouse counterpart in more detail. Human and mouse THRAP2/Thrap2 span a genomic region of about 310 and >170 kilobases (kb), and both contain 31 exons. Corresponding transcripts are approximately 9.5 kb long. Their open reading frames code for proteins of 2210 and 2203 amino acids, which are 93% identical. By northern blot analysis, human and mouse THRAP2/Thrap2 genes showed ubiquitous expression. Transcripts were most abundant in human skeletal muscle and in mouse heart. THRAP2 protein is 56% identical to human TRAP240, which belongs to the thyroid hormone receptor associated protein (TRAP) complex and is evolutionary conserved up to yeast. This complex is involved in transcriptional regulation and is believed to serve as adapting interface between regulatory proteins bound to specific DNA sequences and RNA polymerase II.
A new sodium channel {alpha}-subunit gene (Scn9a) from Schwann cells maps to the Scn1a, Scn2a, Scn3a cluster of mouse chromosome 2
Energy Technology Data Exchange (ETDEWEB)
Beckers, M.C.; Ernst, E.; Gros, P. [McGill Univ., Montreal (Canada)
We have used a total of 27 AXB/BXA recombinant inbred mouse strains to determine the chromosomal location of a newly identified gene encoding an {alpha}-subunit isoform of the sodium channel from Schwann cells, Scn9a. Linkage analysis established that Scn9a mapped to the proximal segment of mouse chromosome 2. The segregation of restriction fragment length polymorphisms in 145 progeny from a Mus spretus x C57BL/6J backcross indicates that Scn9a is very tightly linked to Scn1a (gene encoding the type I sodium channel {alpha}-subunit of the brain) and forms part of a cluster of four Scna genes located on mouse chromosome 2. 17 refs., 1 fig., 3 tabs.
Stage-specific damage to synaptonemal complexes and metaphase chromosomes induced by X rays in male mouse germ cells
International Nuclear Information System (INIS)
Backer, L.C.; Sontag, M.R.; Allen, J.W.
Synaptonemal complexes (SCs) reveal mutagen-induced effects in germ cell meiotic chromosomes. The study was aimed at characterizing relationships between SC and metaphase I chromosome damage following radiation exposure at various stages of spermatogenesis. Male mice were irradiated with doses of 0, 2, or 4 Gy, and spermatocytes were harvested at times consistent with earlier exposures as spermatogonial stem cells, preleptotene cells (premeiotic DNA synthesis), or meiotic prophase cells. After stem-cell exposure, twice as many rearrangements were observed in SCs as in metaphase I chromosomes. Irradiation during premeiotic DNA synthesis resulted in dose-related increases in SC breakage and rearrangements (including novel forms) and in metaphase chromosomal aberrations. Following prophase exposure, various types and levels of SC and metaphase damage were observed. Irradiation of zygotene cells led to high frequencies of chromosome multivalents in metaphase I without a correspondingly high level of damage in preceding prophase SCs. Thus, irradiation of premeiotic and meiotic cells results in variable relationships between SC and metaphase chromosome damage
A comparative study on the frequencies of radiation-induced chromosome aberrations in the somatic and germ cells in mouse and monkey
International Nuclear Information System (INIS)
Sobels, F.H.
Two systems were mainly used for studying the relationship between radiation induced chromosome aberration frequencies in somatic and germ cells. The first consists of reciprocal translocation induced in bone-marrow cells of mice compared to reciprocal translocation induced spermatogonia (scored in descending spermatocytes) of the same mice. Dose-response curves for induced aberrations in both cell types (0-100-200-300-400-500 and 600 R X-rays) and dose rate effects indicated that (130-1.92-0.0287 R/min) of a 400 R γ-ray exposure of the two cell types mitotically dividing germ cells respond to radiation similarly to mitotic dividing germ cells. Clonal proliferation or selective elimination of aberration-carrying cells, and other post-irradiation factors can, however, cause great differences in absolute aberration frequencies. A similar study was attempted, using the rhesus monkey as a second system. Its bone-marrow cells were proved unsuitable for induced reciprocal translocations. Stimulated peripheral blood lymphocytes were studied instead. Following 100, 200 and 300 R of X-rays, the frequencies of induced dicentric chromosomes were compared to those of induced reciprocal translocations in spermatogonia. Human peripheral blood was studied similarly. It was concluded that: (a) The absolute frequencies of chromosome aberrations in somatic and germ cells of the rhesus monkey are low compared to most other mammalian species. (b) The ratio between dicentric frequencies and reciprocal translocation frequencies at 100 R and 200 R differed significantly from 4:1 reported for mouse and Chinese hamster and 2:1 for marmoset and man. (c) Although the numbers of 'effective chromosome arms' in man and rhesus monkey are similar (81 vs 83), the rhesus monkey showed at all doses a lower rate of induction of dicentrics in blood lymphocytes than man, reaching statistical significance at the 300 R level
Mapping of the X-linked cataract (Xcat) mutation, the gene implicated in the Nance Horan syndrome, on the mouse X chromosome.
Stambolian, D; Favor, J; Silvers, W; Avner, P; Chapman, V; Zhou, E
The Xcat mutation in the mouse, an X-linked inherited disorder, is characterized by the congenital onset of cataracts. The cataracts have morphologies similar to those of cataracts found in the human Nance Horan (X-linked cataract dental) syndrome, suggesting that Xcat is an animal model for Nance Horan. The Xcat mutation provides an opportunity to investigate, at the molecular level, the pathogenesis of cataract. As a first step to cloning the Xcat gene, we report the localization of the Xcat mutation with respect to known molecular markers on the mouse X chromosome. Back-cross progeny carrying the Xcat mutation were obtained from an interspecific cross. Genomic DNA from each mouse was subjected to Southern and PCR analysis to identify restriction fragment length polymorphisms and simple sequence length polymorphisms, respectively. Our results refine the location of Xcat to a 2-cM region, eliminate several genes from consideration as the Xcat mutation, identify molecular probes tightly linked with Xcat, and suggest candidate genes responsible for the Xcat phenotype.
The secretory KCa1.1 channel localises to crypts of distal mouse colon: functional and molecular evidence
DEFF Research Database (Denmark)
Sørensen, Mads Vaarby; Strandsby, Anne Bystrup; Larsen, Casper Kornbech
The colonic epithelium absorbs and secretes electrolytes and water. Ion and water absorption occurs primarily in surface cells, whereas crypt cells perform secretion. Ion transport in distal colon is regulated by aldosterone, which stimulates both Na+ absorption and K+ secretion. The electrogenic...
Effect of vitamin E on preovulatory stage irradiated female mouse expressed as chromosomal abnormalities in generated embryos
International Nuclear Information System (INIS)
Salimi, M.; Mozdarani, H.
The present study has been carried out to investigate the effects of preovulatory stage gamma-irradiation of female mice in the absence or presence of vitamin E on numerical chromosome abnormalities in 8-cell embryos after mating with non- irradiated males. Materials and Methods: The 8-11 weeks adult female NMRl mice were whole body irradiated at preovulatory stage (post PMSG injection and about 12-18 hours before Injecting HCG) with 4 Gy gamma-rays generated from a cobalt-60 source alone or in combination with 200 IU/kg vitamin E, intraperitoneally administered one hour prior to irradiation. Soon after HCG injection super ovulated irradiated females were mated with non-irradiated males. About 68-h post coitus (p.c), 8-cell embryos were flushed from the oviducts of pregnant mice and were fixed on slides using standard methods in order to screen for metaphase spreads and numerical chromosome abnormalities. Results: In control embryos, 8% of metaphase plates were aneuploidy whereas in preovulatory stage irradiated female mice, about 50% of metaphase plates of embryos showed numerical chromosome aberrations (P nd meiotic division. Reduction of the frequency of chromosome aberrations in the presence of vitamin E is probably due to antioxidant effects of this vitamin, and scavenging free radicals induced by gamma-rays in mice oocytes' environment
Stage specificity and dose-response relationships for chromosome aberrations induced in mouse primary spermatocytes following X-irradiation
Energy Technology Data Exchange (ETDEWEB)
Matsuda, Y.; Tobari, I.; Utsugi, T.
In this study, dose-response relationships were examined for chromosome aberrations observed at diakinesis-metaphase I of spermatocytes with X-irradiation at various stages of meiosis (diplotene, mid-pachytene, zygotene and leptotene). The frequencies of cells with X-ray-induced chromosome aberrations increased with dose at all stages in the applied range of 0.5-3.0 Gy and tended to increase as the irradiated stages descended after leptotene stage. In three stages, the frequencies increased exponentially with dose, but the rates of induction of chromosome breaks were markedly different depending on the stages at which spermatocytes were irradiated with X-rays. The rate of induction was the highest at diplotene and the lowest at leptotene, suggesting that diplotene spermatocytes had the highest radiosensitivity to the induction of chromosome breaks, followed by pachytene, zygotene and leptotene spermatocytes in that order. The dose-response relationships fitted well to linear equations for deletion-type aberrations at each stage, and to linear-quadratic equations for exchange-type aberrations at all stages except for leptotene. At leptotene, the chromatid exchanges were hardly observed, the aberrations being mainly consisted of iso-chromatid fragments. On the contrary, chromatid exchanges and iso-chromatide deletions were mainly observed at later stages (zygotene-diplotene).
Chromosomal aberrations induced by 12C6+ ions and 6Co γ-rays in mouse immature oocytes
International Nuclear Information System (INIS)
Zhang Hong; Duan Xin; Yuan Zhigang; Li Wenjian; Zhou Guangming; Zhou Qingming; Bing Liu; Min Fengling; Li Xiaoda; Xie Yi
The ovaries of Kun-Ming strain mice (3 weeks) were irradiated with different doses of 12 C 6+ ion or 6 Co γ-ray. Chromosomal aberrations were analyzed in metaphase II oocytes at 7 weeks after irradiation. The relative biological effectiveness (RBE) of 12 C 6+ ion was calculated with respect to 6 Co γ-ray for the induction of chromosomal aberrations. The 12 C 6+ ion and 6 Co γ-ray dose-response relationships for chromosomal aberrations were plotted by linear quadratic models. The data showed that there was a dose-related increase in frequency of chromosomal aberrations in all the treated groups compared to controls. The RBE values for 12 C 6+ ions relative to 6 Co γ-rays were 2.49, 2.29, 1.57, 1.42 or 1.32 for the doses of 0.5, 1.0, 2.0, 4.0 or 6.0 Gy, respectively. Moreover, a different distribution of the various types of aberrations has been found for 12 C 6+ ion and 6 Co γ-ray irradiations. The dose-response relationships for 12 C 6+ ion and 6 Co γ-ray exhibited positive correlations. The results from the present study may be helpful for assessing genetic damage following exposure of immature oocytes to ionizing radiation
Genes on chromosomes 1 and 4 in the mouse are associated with repair of radiation-induced chromatin damage.
Potter, M; Sanford, K K; Parshad, R; Tarone, R E; Price, F M; Mock, B; Huppi, K
Early-passage skin fibroblasts from different inbred and congenic strains of mice were X-irradiated (1 Gy), and the number of chromatid breaks was determined at 2.0 h after irradiation. The cells from DBA/2N, C3H/HeN, STS/A, C57BL/6N, BALB/cJ, and AKR/N had 25 to 42 chromatid breaks per 100 metaphase cells (efficient repair phenotype). NZB/NJ had greater than 78 and BALB/cAn had 87 to 110 chromatid breaks per 100 cells (inefficient repair phenotype). Differences between BALB/cAn and BALB/c. DBA/2 congenic strains which carry less than 1% of the DBA/2 genome indicate that two genes, one on chromosome 1 linked to bcl-2-Pep-3 and the other on chromosome 4 closely linked to Fv-1, affect the efficiency with which the cells repair radiation-induced chromatin damage.
The contribution of p53 and Y chromosome long arm genes to regulation of apoptosis in mouse testis.
Lech, Tomasz; Styrna, Józefa; Kotarska, Katarzyna
Apoptosis of excessive or defective germ cells is a natural process occurring in mammalian testes. Tumour suppressor protein p53 is involved in this process both in developing and adult male gonads. Its contribution to testicular physiology is known to be modified by genetic background. The aim of this study was to evaluate the combined influence of the p53 and Y chromosome long arm genes on male germ cell apoptosis. Knockout of the transformation related protein 53 (Trp53) gene was introduced into congenic strains: B10.BR (intact Y chromosome) and B10.BR-Ydel (Y chromosome with a deletion in the long arm). The level of apoptosis in the testes of 19-day-old and 3-month-old male mice was determined using the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate in situ nick-end labelling (TUNEL) method. The study revealed that although p53 is involved in germ cell apoptosis in peripubertal testes, this process can also be mediated by p53-independent mechanisms. However, activation of p53-independent apoptotic pathways in the absence of the p53 protein requires engagement of the multicopy Yq genes and was not observed in gonads of B10.BR-Ydel-p53-/- males. The role of Yq genes in the regulation of testicular apoptosis seems to be restricted to the initial wave of spermatogenesis and is not evident in adult gonads. The study confirmed, instead, that p53 does participate in spontaneous apoptosis in mature testes.
Radiation susceptibility of the mouse smalleye mutants, Del(2)Sey3Hpax6 and Del(2)Sey4Hpax6, which delete the chromosome 2 middle regions
International Nuclear Information System (INIS)
Nitta, Y.; Hoshi, M.; Yoshida, K.; Yamate, J.; Peters, J.; Cattanach, B.M.
Full text: LOH at the chromosome 2 middle regions is common in the radiation-induced mouse acute myeloid leukemia (AML). To identify the suppressor or the modifier gene of AML at this region, the mouse deletion mutants, Del(2)Sey3H pax6 and Del(2)Sey3H pax6 could be the good models, as they deleted the chromosome 2 middle regions hemizygously. The allele of the partially deleted chromosome 2 was paternally generated and maintained hemizygously. The exact deleted regions of the two mutants were mapped by the PCR-based detection of polymorphism of the STS markers. The length of the deletions was 3.01Mb and 10.11MB for Del(2)Sey3H pax6 and Del(2)Sey3H pax6 , respectively. For the induction of tumors, a radiation, 3.0Gy of Co-60 and a chemical carcinogen, N-methyl-N-nitrosourea were applied to the mutants. Their tumorigenicity was compared with those of control as well as normal sibs by the Kaplan-Meier analysis. Both mutants were found to predispose to small intestinal tumors. Intestinal tumors developed spontaneously with the incidence of 30%. The radiation and the chemical accelerated the malignancy and increased the incidence of the intestinal tumors. Radiation shortened the latency of AML development in the Del(2)Sey3H pax6 mutant but not in the Del(2)Sey3H pax6 . Spontaneous AML has not been observed, nor any increase in the incidence of induced AMLs. The commonly deleted region of the two mutants, the 3.01Mb region, must be critical for the development of tumors and the high susceptibility to radiation. The role of Pax6 gene should be considered in the intestinal tumorigenesis, as the Pax6 gene plays an important role in the pancreas development during the embryogenesis. The Wt1, a tumor suppressor gene, which is deleted hemizygously in these mutants as well. The screening of homozygous deletion has been started using the induced as well as spontaneously developed tumors
Chromosomal aberrations induced by X-rays in two mouse lymphoma (L5178Y) sublines of different radiosensitivity
International Nuclear Information System (INIS)
Bocian, E.; Bouzyk, E.; Rosiek, O.; Ziemba-Zoltowska, B.
Two mouse lymphoma cell strains, L5178-S and L5178-R, were pulse labelled for 20 min with tritiated thymidine, and then irradiated with 1 Gy of X-rays (180 kV at 0.34 Gy/min). It was found that the cells of the radiation-sensitive subline (S) displayed a higher frequency of chromatid aberrations following radiation exposure, than cells of the radiation-resistant subline (R). (U.K.)
Chromosomal aberrations induced by X-rays in two mouse lymphoma (L5178Y) sublines of different radiosensitivity
Energy Technology Data Exchange (ETDEWEB)
Bocian, E.; Bouzyk, E.; Rosiek, O.; Ziemba-Zoltowska, B. (Institute of Nuclear Research, Warsaw (Poland))
Two mouse lymphoma cell strains, L5178-S and L5178-R, were pulse labelled for 20 min with tritiated thymidine, and then irradiated with 1 Gy of X-rays (180 kV at 0.34 Gy/min). It was found that the cells of the radiation-sensitive subline (S) displayed a higher frequency of chromatid aberrations following radiation exposure, than cells of the radiation-resistant subline (R).
Mouse model for Usher syndrome: linkage mapping suggests homology to Usher type I reported at human chromosome 11p15.
Heckenlively, J R; Chang, B; Erway, L C; Peng, C; Hawes, N L; Hageman, G S; Roderick, T H
Usher syndrome is a group of diseases with autosomal recessive inheritance, congenital hearing loss, and the development of retinitis pigmentosa, a progressive retinal degeneration characterized by night blindness and visual field loss over several decades. The causes of Usher syndrome are unknown and no animal models have been available for study. Four human gene sites have been reported, suggesting at least four separate forms of Usher syndrome. We report a mouse model of type I Usher syndr...
High-intensity exercise training increases the diversity and metabolic capacity of the mouse distal gut microbiota during diet-induced obesity.
Denou, Emmanuel; Marcinko, Katarina; Surette, Michael G; Steinberg, Gregory R; Schertzer, Jonathan D
Diet and exercise underpin the risk of obesity-related metabolic disease. Diet alters the gut microbiota, which contributes to aspects of metabolic disease during obesity. Repeated exercise provides metabolic benefits during obesity. We assessed whether exercise could oppose changes in the taxonomic and predicted metagenomic characteristics of the gut microbiota during diet-induced obesity. We hypothesized that high-intensity interval training (HIIT) would counteract high-fat diet (HFD)-induced changes in the microbiota without altering obesity in mice. Compared with chow-fed mice, an obesity-causing HFD decreased the Bacteroidetes-to-Firmicutes ratio and decreased the genetic capacity in the fecal microbiota for metabolic pathways such as the tricarboxylic acid (TCA) cycle. After HFD-induced obesity was established, a subset of mice were HIIT for 6 wk, which increased host aerobic capacity but did not alter body or adipose tissue mass. The effects of exercise training on the microbiota were gut segment dependent and more extensive in the distal gut. HIIT increased the alpha diversity and Bacteroidetes/Firmicutes ratio of the distal gut and fecal microbiota during diet-induced obesity. Exercise training increased the predicted genetic capacity related to the TCA cycle among other aspects of metabolism. Strikingly, the same microbial metabolism indexes that were increased by exercise were all decreased in HFD-fed vs. chow diet-fed mice. Therefore, exercise training directly opposed some of the obesity-related changes in gut microbiota, including lower metagenomic indexes of metabolism. Some host and microbial pathways appeared similarly affected by exercise. These exercise- and diet-induced microbiota interactions can be captured in feces. Copyright © 2016 the American Physiological Society.
Microclones derived from the mouse chromosome 7 D-E bands map within the proximal region of the c14CoS deletion in albino mutant mice
International Nuclear Information System (INIS)
Toenjes, R.R.W.; Weith, A.; Rinchik, E.M.; Winking, H.; Carnwath, J.W.; Kaliner, B.; Paul, D.
A group of radiation-induced perinatal-lethal deletions that include the albino (c) locus on mouse chromosome 7 causes failure of expression of various hepatocyte-specific genes when homozygous. The transcription of such genes could be controlled in trans by a regulatory gene(s) located within the proximal region of the C14CoS deletion. To identify this potential regulatory gene, a microclone library was established from microdissected D and E bands of chromosome 7. Three nonoverlapping microclones (E305, E336B, and E453B) hybridizing with wildtype but not with C14CoS/C14CoS DNA were isolated. E336B represents a single-copy DNA fragment, whereas E305 and E453B hybridized with 3 and 10 EcoRI DNA restriction fragments, respectively. All fragments map exclusively within the deletion. The microclones hybridized to DNA of viable C6H/C14CoS deletion heterozygotes but not to DNA of homozygotes for the lethal mutation c10R75M, which belongs to the same complementation group as c14CoS. DNA of viable homozygous mutant C62DSD, which carries a deletion breakpoint proximal to that of c6H, hybridized only with E453B. This microclone identified 6 EcoRI restriction fragments in C62DSD/C62DSD DNA. The results demonstrate that of the isolated microclones, E453B identifies a locus (D7RT453B) that maps closest to the hsdr-1 (hepatocyte-specific developmental regulation) locus, which maps between the proximal breakpoints of deletions c10R75M and c62DSD
Development of a multiple-gene-loading method by combining multi-integration system-equipped mouse artificial chromosome vector and CRISPR-Cas9.
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Kazuhisa Honma
Full Text Available Mouse artificial chromosome (MAC vectors have several advantages as gene delivery vectors, such as stable and independent maintenance in host cells without integration, transferability from donor cells to recipient cells via microcell-mediated chromosome transfer (MMCT, and the potential for loading a megabase-sized DNA fragment. Previously, a MAC containing a multi-integrase platform (MI-MAC was developed to facilitate the transfer of multiple genes into desired cells. Although the MI system can theoretically hold five gene-loading vectors (GLVs, there are a limited number of drugs available for the selection of multiple-GLV integration. To overcome this issue, we attempted to knock out and reuse drug resistance genes (DRGs using the CRISPR-Cas9 system. In this study, we developed new methods for multiple-GLV integration. As a proof of concept, we introduced five GLVs in the MI-MAC by these methods, in which each GLV contained a gene encoding a fluorescent or luminescent protein (EGFP, mCherry, BFP, Eluc, and Cluc. Genes of interest (GOI on the MI-MAC were expressed stably and functionally without silencing in the host cells. Furthermore, the MI-MAC carrying five GLVs was transferred to other cells by MMCT, and the resultant recipient cells exhibited all five fluorescence/luminescence signals. Thus, the MI-MAC was successfully used as a multiple-GLV integration vector using the CRISPR-Cas9 system. The MI-MAC employing these methods may resolve bottlenecks in developing multiple-gene humanized models, multiple-gene monitoring models, disease models, reprogramming, and inducible gene expression systems.
Cytogenetic and molecular studies on a recombinant human X chromosome: implications for the spreading of X chromosome inactivation
International Nuclear Information System (INIS)
Mohandas, T.; Geller, R.L.; Yen, P.H.; Rosendorff, J.; Bernstein, R.; Yoshida, A.; Shapiro, L.J.
A pericentric inversion of human X chromosome and a recombinant X chromosome [rec(X)] derived from crossing-over within the inversion was identified in a family. The rec(X) had a duplication of the segment Xq26.3 → Xqter and a deletion of Xp22.3 → Xpter and was interpreted to be Xqter → Xq26.3::Xp22.3 → Xqter. To characterize the rec(X) chromosome, dosage blots were done on genomic DNA from carriers of this rearranged X chromosome using a number of X chromosome probes. Results showed that anonymous sequences from the distal end of the long arm to which probes 4D8, Hx120A, DX13, and St14 bind as well as the locus for glucose-6-phosphate dehydrogenase (G6PD) wee duplicated on the rec(X). Mouse-human cell hybrids were constructed that retained the rec(X) in the active or inactive state. Analyses of these hybrid clones for markers from the distal short arm of the X chromosome showed that the rec(X) retained the loci for steroid sulfatase (STS) and the cell surface antigen 12E7 (MIC2); but not the pseudoautosomal sequence 113D. These molecular studies confirm that the rec(X) is a duplication-deficiency chromosome as expected. In the inactive state in cell hybrids, STS and MIC2 (which usually escape X chromosome inactivation) were expressed from the rec(X), whereas G6PD was not. Therefore, in the rec(X) X chromosome inactivation has spread through STS and MIC2 leaving these loci unaffected and has inactivated G6PD in the absence of an inactivation center in the q26.3 → qter region of the human X chromosome. The mechanism of spreading of inactivation appears to operate in a sequence-specific fashion. Alternatively, STS and MIC2 may have undergone inactivation initially but could not be maintained in an inactive state
... this disorder. Alternative Names Renal tubular acidosis - distal; Renal tubular acidosis type I; Type I RTA; RTA - distal; Classical RTA Images Kidney anatomy Kidney - blood and urine flow References Bose A, Monk RD, Bushinsky DA. Kidney ...
Potassium secretion in mammalian distal colon
DEFF Research Database (Denmark)
Sørensen, Mads Vaarby
Epithelial organs adjust the "inner milieu" of the body and are crucial for all homeostatic processes. Epithelial transport of different solutes and water is regulated phenomena. The regulation processes include both long term hormonal regulation and short term local agonist mediated regulation....... This research project is the summary of 3 original papers addressing the functional role of different regulating factors on ion transport in mouse distal colon. The first paper addresses the effect of luminal nucleotides on electrogenic Na+ absorption. The distal colon, like the distal nephron is an aldosterone......-sensitive tissue and participates in the regulation of Na+ excretion. In the distal nephron it was found that luminal nucleotides inhibit ENaC-mediated Na+ absorption. Here it was addressed whether luminal nucleotides regulate Na+ absorption and if so, which of the known luminal P2 receptors are involved. Using...
Mapping of the mouse actin capping protein {alpha} subunit genes and pseudogenes
Energy Technology Data Exchange (ETDEWEB)
Hart, M.C.; Korshunova, Y.O.; Cooper, J.A. [Washington Univ. School of Medicine, St. Louis, MO (United States)
Capping protein (CP), a heterodimer of {alpha} and {beta} subunits, is found in all eukaryotes. CP binds to the barbed ends of actin filaments in vitro and controls actin assembly and cell motility in vivo. Vertebrates have three {alpha} isoforms ({alpha}1, {alpha}2, {alpha}3) produced from different genes, whereas lower organisms have only one gene and one isoform. We isolated genomic clones corresponding to the a subunits of mouse CP and found three {alpha}1 genes, two of which are pseudogenes, and a single gene for both {alpha}2 and {alpha}3. Their chromosomal locations were identified by interspecies backcross mapping. The {alpha}1 gene (Cappa1) mapped to Chromosome 3 between D3Mit11 and D3Mit13. The {alpha}1 pseudogenes (Cappa1-ps1 and Cappa1-ps2) mapped to Chromosomes 1 and 9, respectively. The {alpha}2 gene (Cappa2) mapped to Chromosome 6 near Ptn. The {alpha}3 gene (Cappa3) also mapped to Chromosome 6, approximately 68 cM distal from Cappa2 near Kras2. One mouse mutation, de, maps in the vicinity of the {alpha}1 gene. No known mouse mutations map to regions near the {alpha}2 or {alpha}3 genes. 29 refs., 3 figs., 1 tab.
Cytogenetic and genetic studies of radiation-induced chromosome damage in mouse oocytes. Part 1. Numerical and structural chromosome anomalies in metaphase II oocytes, pre- and post-implantation embryos
International Nuclear Information System (INIS)
Tease, Charles; Fisher, Graham
The incidences of X-ray induced numerical and structural chromosome anomalies were screened in a range of developmental stages from metaphase II oocytes through to post-implantation embryos. Following 1 Gy of acute X-rays to immediately preovulatory stage oocytes, the rate of hyperploidy (chromosome gain) was found to be elevated over levels in unirradiated controls, at metaphase II, in 1-cell and 3.5 day pre-implantation embryos but not in 8.5 day post-implantation foetuses. In the latter, however, the frequency of mosaicism was significantly increased. A similar response of an increase in mosaicism but not in hyperploidy in 8.5 day post-implantation embryos was also found after irradiation of dictyate stage oocytes with 4 Gy of acute X-rays. Significantly elevated frequencies of structural chromosome anomalies were present in metaphase II oocytes and pre-implantation embryonic stages, but could not be detected in block-stained chromosome preparations from 8.5 day post-implantation foetuses. However, analysis of chromosome preparations after G-banding showed that almost 14% of 14.5 day foetuses carried a chromosome rearrangement after 1 Gy of X-rays to immediately preovulatory stage oocytes. Overall, our data indicate that the presence of radiation-induced chromosome gains are incompatible with embryonic survival but that a proportion of embryos with structural chromosome damage develop past mid-gestation. These latter embryos are therefore potentially capable of contributing to the genetic burden of the next generation
Chromosome Y variants from different inbred mouse strains are linked to differences in the morphologic and molecular responses of cardiac cells to postpubertal testosterone
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Churchill Gary A
Full Text Available Abstract Background We have reported previously that when chromosome Y (chrY from the mouse strain C57BL/6J (ChrYC57 was substituted for that of A/J mice (ChrYA, cardiomyocytes from the resulting "chromosome substitution" C57BL/6J-chrYA strain were smaller than that of their C57BL/6J counterparts. In reverse, when chrYA from A/J mice was substituted for that of chrYC57, cardiomyocytes from the resulting A/J-chrYC57 strain were larger than in their A/J counterparts. We further used these strains to test whether: 1 the origin of chrY could also be linked to differences in the profile of gene expression in the hearts of adult male mice, and 2 post-pubertal testosterone could play a role in the differential morphologic and/or molecular effects of chrYC57 and chrYA. Results The increased size of cardiomyocytes from adult male C57BL/6J mice compared to C57BL/6J-chrYA resulted from the absence of hypertrophic effects of post-pubertal testosterone on cells from the latter strain. However, gene profiling revealed that the latter effect could not be explained on the basis of an insensitivity of cells from C57BL/6J-chrYA to androgens, since even more cardiac genes were affected by post-pubertal testosterone in C57BL/6J-chrYA hearts than in C57BL/6J. By testing for interaction between the effects of surgery and strain, we identified 249 "interaction genes" whose expression was affected by post-pubertal testosterone differentially according to the genetic origin of chrY. These interaction genes were found to be enriched within a limited number of signaling pathways, including: 1 p53 signaling, which comprises the interacting genes Ccnd1, Pten and Cdkn1a that are also potential co-regulators of the androgen receptors, and 2 circadian rhythm, which comprises Arntl/Bmal1, which may in turn regulate cell growth via the control of Cdkn1a. Conclusion Although post-pubertal testosterone increased the size of cardiomyocytes from male C56BL/6J mice but not that from
Polytene chromosome map and inversion polymorphism in Drosophila mediopunctata
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Galina Ananina
Full Text Available Drosophila mediopunctata belongs to the tripunctata group, and is one of the commonest Drosophila species collected in some places in Brazil, especially in the winter. A standard map of the polytene chromosomes is presented. The breakpoints of the naturally occurring chromosomal rearrangements are marked on the map. The distribution of breaking points through the chromosomes of D. mediopunctata is apparently non-random. Chromosomes X, II and IV show inversion polymorphisms. Chromosome II is the most polymorphic, with 17 inversions, 8 inversions in the distal region and 9 in the proximal region. Chromosome X has four different gene arrangements, while chromosome IV has only two.
Jazayeri, Leila; Klausner, Jill Q; Chang, James
Hand surgeons have been hesitant to perform distal digital replantation because of the technical challenges and the perception of a high cost-to-benefit ratio. Recent studies, however, have shown high survival rates and excellent functional and aesthetic results, providing renewed enthusiasm for distal replantation. The authors reviewed the literature and summarize key points regarding the surgical treatment, perioperative care, and outcomes of distal digital replantation. They describe specific techniques and considerations for surgical repair in each of four distal zones as described by Sebastin and Chung. Zone 1A replantation involves an artery-only anastomosis of a longitudinal pulp artery. Venous anastomosis first becomes possible in zone 1B. Zone 1C involves periarticular amputations where arthrodesis of the distal interphalangeal joint is usually indicated. Repair of the artery, vein, and nerve is technically optimal in zone 1D, where venous anastomosis should be performed. Overall, survival rates for distal digital replantation are similar to those reported for more proximal replantation. The literature reports good outcomes regarding nail salvage, fingertip sensibility, and range of motion, with restoration of length and aesthetic appearance. Distal replantation performed at institutions that specialize in microsurgery and specifically tailored to the level of injury is associated with good survival, function, and patient satisfaction and superior aesthetic outcome. More prospective data are needed to evaluate the cost of treatment, psychological outcomes, and functional outcomes of distal replantation compared with revision amputation.
Genome sequencing and transcriptome analysis of Trichoderma reesei QM9978 strain reveals a distal chromosome translocation to be responsible for loss of vib1 expression and loss of cellulase induction.
Ivanova, Christa; Ramoni, Jonas; Aouam, Thiziri; Frischmann, Alexa; Seiboth, Bernhard; Baker, Scott E; Le Crom, Stéphane; Lemoine, Sophie; Margeot, Antoine; Bidard, Frédérique
The hydrolysis of biomass to simple sugars used for the production of biofuels in biorefineries requires the action of cellulolytic enzyme mixtures. During the last 50 years, the ascomycete Trichoderma reesei , the main source of industrial cellulase and hemicellulase cocktails, has been subjected to several rounds of classical mutagenesis with the aim to obtain higher production levels. During these random genetic events, strains unable to produce cellulases were generated. Here, whole genome sequencing and transcriptomic analyses of the cellulase-negative strain QM9978 were used for the identification of mutations underlying this cellulase-negative phenotype. Sequence comparison of the cellulase-negative strain QM9978 to the reference strain QM6a identified a total of 43 mutations, of which 33 were located either close to or in coding regions. From those, we identified 23 single-nucleotide variants, nine InDels, and one translocation. The translocation occurred between chromosomes V and VII, is located upstream of the putative transcription factor vib1 , and abolishes its expression in QM9978 as detected during the transcriptomic analyses. Ectopic expression of vib1 under the control of its native promoter as well as overexpression of vib1 under the control of a strong constitutive promoter restored cellulase expression in QM9978, thus confirming that the translocation event is the reason for the cellulase-negative phenotype. Gene deletion of vib1 in the moderate producer strain QM9414 and in the high producer strain Rut-C30 reduced cellulase expression in both cases. Overexpression of vib1 in QM9414 and Rut-C30 had no effect on cellulase production, most likely because vib1 is already expressed at an optimal level under normal conditions. We were able to establish a link between a chromosomal translocation in QM9978 and the cellulase-negative phenotype of the strain. We identified the transcription factor vib1 as a key regulator of cellulases in T. reesei whose
Chromosomal and regional localization of the loci for IGKC, IGGC, ALDB, HOXB, GPT, and PRNP in the American mink (Mustela vison): comparisons with human and mouse
DEFF Research Database (Denmark)
Khlebodarova, TM; Malchenko, Sergey; Matveeva, NM
Chromosomal localization of the genes for gamma- and kappa-immunoglobulins (IGGC and IGKC, respectively), aldolase B (ALDB), prion protein (PRNP), homeo box B (HOXB), and glutamate pyruvate transaminase (GPT) were determined with the use of mink-rodent hybrid cells. Analysis of segregation...
A Quantitative Trait Locus (LSq-1) on Mouse Chromosome 7 Is Linked to the Absence of Tissue Loss After Surgical Hindlimb Ischemia
Dokun, Ayotunde O.; Keum, Sehoon; Hazarika, Surovi; Li, Yongjun; Lamonte, Gregory M.; Wheeler, Ferrin; Marchuk, Douglas A.; Annex, Brian H.
Background Peripheral arterial disease (PAD) caused by occlusive atherosclerosis of the lower extremity has 2 major clinical manifestations. Critical limb ischemia is characterized by rest pain and/or tissue loss and has a ≥40% risk of death and major amputation. Intermittent claudication causes pain on walking, has no tissue loss, and has amputation plus mortality rates of 2% to 4% per year. Progression from claudication to limb ischemia is infrequent. Risk factors in most PAD patients overlap. Thus, we hypothesized that genetic variations may be linked to presence or absence of tissue loss in PAD. Methods and Results Hindlimb ischemia (murine model of PAD) was induced in C57BL/6, BALB/c, C57BL/6×BALB/c (F1), F1×BALB/c (N2), A/J, and C57BL/6J-Chr7A/J/NaJ chromosome substitution strains. Mice were monitored for perfusion recovery and tissue necrosis. Genome-wide scanning with polymorphic markers across the 19 murine autosomes was performed on the N2 mice. Greater tissue loss and poorer perfusion recovery occurred in BALB/c than in the C57BL/6 strain. Analysis of 105 N2 progeny identified a single quantitative trait locus on chromosome 7 that exhibited significant linkage to both tissue necrosis and extent of perfusion recovery. Using the appropriate chromosome substitution strain, we demonstrate that C57BL/6-derived chromosome 7 is required for tissue preservation. Conclusions We have identified a quantitative trait locus on murine chromosome 7 (LSq-1) that is associated with the absence of tissue loss in a preclinical model of PAD and may be useful in identifying gene(s) that influence PAD in humans. PMID:18285563
Seppel, G; Lenich, A; Imhoff, A B
Reposition and fixation of unstable distal clavicle fractures with a low profile locking plate (Acumed, Hempshire, UK) in conjunction with a button/suture augmentation cerclage (DogBone/FibreTape, Arthrex, Naples, FL, USA). Unstable fractures of the distal clavicle (Jäger and Breitner IIA) in adults. Unstable fractures of the distal clavicle (Jäger and Breitner IV) in children. Distal clavicle fractures (Jäger and Breitner I, IIB or III) with marked dislocation, injury of nerves and vessels, or high functional demand. Patients in poor general condition. Fractures of the distal clavicle (Jäger and Breitner I, IIB or III) without marked dislocation or vertical instability. Local soft-tissue infection. Combination procedure: Initially the lateral part of the clavicle is exposed by a 4 cm skin incision. After reduction of the fracture, stabilization is performed with a low profile locking distal clavicle plate. Using a special guiding device, a transclavicular-transcoracoidal hole is drilled under arthroscopic view. Additional vertical stabilization is arthroscopically achieved by shuttling the DogBone/FibreTape cerclage from the lateral portal cranially through the clavicular plate. The two ends of the FibreTape cerclage are brought cranially via adjacent holes of the locking plate while the DogBone button is placed under the coracoid process. Thus, plate bridging is achieved. Finally reduction is performed and the cerclage is secured by surgical knotting. Use of an arm sling for 6 weeks. Due to the fact that the described technique is a relatively new procedure, long-term results are lacking. In the short term, patients postoperatively report high subjective satisfaction without persistent pain.
Robertson, Carol
Learning about chromosomes is standard fare in biology classrooms today. However, students may find it difficult to understand the relationships among the "genome", "chromosomes", "genes", a "gene locus", and "alleles". In the simple activity described in this article, which follows the 5E approach…
... and more. Stony Point, NY 10980 Close X Home > Complications & Loss > Birth defects & other health conditions > Chromosomal conditions Chromosomal conditions ... Disorders See also: Genetic counseling , Your family health history Last reviewed: February, 2013 ... labor & premature birth The newborn intensive care unit (NICU) Birth defects & ...
Evaluation of the Genetic and Nutritional Control of Obesity and Type 2 Diabetes in a Novel Mouse Model on Chromosome 7: An Insight into Insulin Signaling and Glucose Homeostasis
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Nelson, S.; Dhar, M.
Obesity is the main cause of type 2 diabetes, accounting for 90-95% of all diabetes cases in the US. Human obesity is a complex trait and can be studied using appropriate mouse models. A novel polygenic mouse model for studying the genetic and environmental contributions to and the physiological ramifications of obesity and related phenotypes is found in specific lines of mice bred and maintained at Oak Ridge National Laboratory. Heterozygous mice with a maternally inherited copy of two radiation-induced deletions in the p region of mouse chromosome 7, p23DFioD and p30PUb, have significantly greater body fat and show hyperinsulinemia compared to the wild-type. A single gene, Atp10c, maps to this critical region and codes for a putative aminophospholipid translocase. Biochemical and molecular studies were initiated to gain insight into obesity and glucose homeostasis in these animals and to study the biological role of Atp10c in creating these phenotypes. Glucose and insulin tolerance tests were standardized for the heterozygous p23DFioD and control mice on a custom-made diet containing 20% protein, 70% carbohydrate, and 10% fat (kcal). Atp10c expression profiles were also generated using Reverse-Transcriptase Polymerase Chain Reaction (RT-PCR). Heterozygous p23DFioD animals showed insulin resistance after receiving a dose of either 0.375 or 0.75 U/kg Illetin R insulin. RT-PCR data also shows differences in Atp10c expression in the mutants versus control mice. Using these standardized biochemical assays, future studies will further the understanding of genetic and nutritional controls of glucose homeostasis and obesity in animal models and subsequently in human populations.
Chromosomal and cytoplasmic context determines predisposition to maternal age-related aneuploidy: brief overview and update on MCAK in mammalian oocytes.
Eichenlaub-Ritter, Ursula; Staubach, Nora; Trapphoff, Tom
It has been known for more than half a century that the risk of conceiving a child with trisomy increases with advanced maternal age. However, the origin of the high susceptibility to nondisjunction of whole chromosomes and precocious separation of sister chromatids, leading to aneuploidy in aged oocytes and embryos derived from them, cannot be traced back to a single disturbance and mechanism. Instead, analysis of recombination patterns of meiotic chromosomes of spread oocytes from embryonal ovary, and of origins and exchange patterns of extra chromosomes in trisomies, as well as morphological and molecular studies of oocytes and somatic cells from young and aged females, show chromosome-specific risk patterns and cellular aberrations related to the chronological age of the female. In addition, analysis of the function of meiotic- and cell-cycle-regulating genes in oogenesis, and the study of the spindle and chromosomal status of maturing oocytes, suggest that several events contribute synergistically to errors in chromosome segregation in aged oocytes in a chromosome-specific fashion. For instance, loss of cohesion may differentially predispose chromosomes with distal or pericentromeric chiasmata to nondisjunction. Studies on expression in young and aged oocytes from human or model organisms, like the mouse, indicate that the presence and functionality/activity of gene products involved in cell-cycle regulation, spindle formation and organelle integrity may be altered in aged oocytes, thus contributing to a high risk of error in chromosome segregation in meiosis I and II. Genes that are often altered in aged mouse oocytes include MCAK (mitotic-centromere-associated protein), a microtubule depolymerase, and AURKB (Aurora kinase B), a protein of the chromosomal passenger complex that has many targets and can also phosphorylate and regulate MCAK localization and activity. Therefore we explored the role of MCAK in maturing mouse oocytes by immunofluorescence
Are There Knots in Chromosomes?
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Jonathan T. Siebert
Full Text Available Recent developments have for the first time allowed the determination of three-dimensional structures of individual chromosomes and genomes in nuclei of single haploid mouse embryonic stem (ES cells based on Hi–C chromosome conformation contact data. Although these first structures have a relatively low resolution, they provide the first experimental data that can be used to study chromosome and intact genome folding. Here we further analyze these structures and provide the first evidence that G1 phase chromosomes are knotted, consistent with the fact that plots of contact probability vs sequence separation show a power law dependence that is intermediate between that of a fractal globule and an equilibrium structure.
[Effect of heterozygosity for insertions of homogeneously stained regions in chromosome 1 of the house mouse on synapsis in meiotic prophase].
Borodin, P M; Ladygina, T Iu; Gorlov, I P
Electron microscope analysis of surface-spread synaptonemal complexes (SC) in oocytes and spermatocytes from double cis heterozygotes for Is(HSR; 1C5)1Icg and Is(HSR; 1E3)2Icg was carried out. Aberrant chromosomes were isolated from the feral population of Mus musculus musculus of Novosibirsk. They contain homogeneously stained regions of total length of about 30% of Chr 1 mitotic metaphase. Heteromorphic bivalents of Chr1 with different lengths of the lateral elements of SC and the loop in the intermedial position were revealed in 4.4% spermatocytes and 20% oocytes of heterozygous animals. The loop size depends on the stage of meiosis: it is maximal at late zygotene and decreases up to disappearance during pachytene.
Cremer, Thomas; Cremer, Marion
Chromosome territories (CTs) constitute a major feature of nuclear architecture. In a brief statement, the possible contribution of nuclear architecture studies to the field of epigenomics is considered, followed by a historical account of the CT concept and the final compelling experimental evidence of a territorial organization of chromosomes in all eukaryotes studied to date. Present knowledge of nonrandom CT arrangements, of the internal CT architecture, and of structural interactions wit...
Scheker, Luis R; Becker, Giles W
Reconstruction of the fingertip distal to the flexor tendon insertion by replantation remains controversial and technically challenging, but the anatomy of the fingertip has been well described and provides help in surgical planning. The open-book surgical technique is described with potential complications and is illustrated with clinical cases. Copyright © 2011 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.
International Nuclear Information System (INIS)
Ishii, Yutaka
Chromosomal aberrations are classified into two types, chromosome-type and chromatid-type. Chromosom-type aberrations include terminal deletion, dicentric, ring and interstitial deletion, and chromatid-type aberrations include achromatic lesion, chromatid deletion, isochromatid deletion and chromatid exchange. Clastogens which induce chromosomal aberration are divided into ''S-dependent'' agents and ''S-independent''. It might mean whether they can induce double strand breaks independent of the S phase or not. Double strand breaks may be the ultimate lesions to induce chromosomal aberrations. Caffeine added even in the G 2 phase appeared to modify the frequency of chromatid aberrations induced by X-rays and mitomycin C. Those might suggest that the G 2 phase involves in the chromatid aberration formation. The double strand breaks might be repaired by ''G 2 repair system'', the error of which might yield breakage types of chromatid aberrations and the by-pass of which might yield chromatid exchanges. Chromosome-type aberrations might be formed in the G 1 phase. (author)
Distal radioulnar joint injuries
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Binu P Thomas
Full Text Available Distal radioulnar joint is a trochoid joint relatively new in evolution. Along with proximal radioulnar joint , forearm bones and interosseous membrane, it allows pronosupination and load transmission across the wrist. Injuries around distal radioulnar joint are not uncommon, and are usually associated with distal radius fractures,fractures of the ulnar styloid and with the eponymous Galeazzi or Essex_Lopresti fractures. The injury can be purely involving the soft tissue especially the triangular fibrocartilage or the radioulnar ligaments.The patients usually present with ulnar sided wrist pain, features of instability, or restriction of rotation. Difficulty in carrying loads in the hand is a major constraint for these patients. Thorough clinical examination to localize point of tenderness and appropriate provocative tests help in diagnosis. Radiology and MRI are extremely useful, while arthroscopy is the gold standard for evaluation. The treatment protocols are continuously evolving and range from conservative, arthroscopic to open surgical methods. Isolated dislocation are uncommon. Basal fractures of the ulnar styloid tend to make the joint unstable and may require operative intervention. Chronic instability requires reconstruction of the stabilizing ligaments to avoid onset of arthritis. Prosthetic replacement in arthritis is gaining acceptance in the management of arthritis.
The endocrine stress response is linked to one specific locus on chromosome 3 in a mouse model based on extremes in trait anxiety
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Gonik Mariya
Full Text Available Abstract Background The hypothalamic-pituitary-adrenal (HPA axis is essential to control physiological stress responses in mammals. Its dysfunction is related to several mental disorders, including anxiety and depression. The aim of this study was to identify genetic loci underlying the endocrine regulation of the HPA axis. Method High (HAB and low (LAB anxiety-related behaviour mice were established by selective inbreeding of outbred CD-1 mice to model extremes in trait anxiety. Additionally, HAB vs. LAB mice exhibit comorbid characteristics including a differential corticosterone response upon stress exposure. We crossbred HAB and LAB lines to create F1 and F2 offspring. To identify the contribution of the endocrine phenotypes to the total phenotypic variance, we examined multiple behavioural paradigms together with corticosterone secretion-based phenotypes in F2 mice by principal component analysis. Further, to pinpoint the genomic loci of the quantitative trait of the HPA axis stress response, we conducted genome-wide multipoint oligogenic linkage analyses based on Bayesian Markov chain Monte Carlo approach as well as parametric linkage in three-generation pedigrees, followed by a two-dimensional scan for epistasis and association analysis in freely segregating F2 mice using 267 single-nucleotide polymorphisms (SNPs, which were identified to consistently differ between HAB and LAB mice as genetic markers. Results HPA axis reactivity measurements and behavioural phenotypes were represented by independent principal components and demonstrated no correlation. Based on this finding, we identified one single quantitative trait locus (QTL on chromosome 3 showing a very strong evidence for linkage (2ln (L-score > 10, LOD > 23 and significant association (lowest Bonferroni adjusted p -28 to the neuroendocrine stress response. The location of the linkage peak was estimated at 42.3 cM (95% confidence interval: 41.3 - 43.3 cM and was shown to be in
Cloning and analysis of the mouse Fanconi anemia group A cDNA and an overlapping penta zinc finger cDNA.
Wong, J C; Alon, N; Norga, K; Kruyt, F A; Youssoufian, H; Buchwald, M
Despite the cloning of four disease-associated genes for Fanconi anemia (FA), the molecular pathogenesis of FA remains largely unknown. To study FA complementation group A using the mouse as a model system, we cloned and characterized the mouse homolog of the human FANCA cDNA. The mouse cDNA (Fanca) encodes a 161-kDa protein that shares 65% amino acid sequence identity with human FANCA. Fanca is located at the distal region of mouse chromosome 8 and has a ubiquitous pattern of expression in embryonic and adult tissues. Expression of the mouse cDNA in human FA-A cells restores the cellular drug sensitivity to normal levels. Thus, the expression pattern, protein structure, chromosomal location, and function of FANCA are conserved in the mouse. We also isolated a novel zinc finger protein, Zfp276, which has five C(2)H(2) domains. Interestingly, Zfp276 is situated in the Fanca locus, and the 3'UTR of its cDNA overlaps with the last four exons of Fanca in a tail-to-tail manner. Zfp276 is expressed in the same tissues as Fanca, but does not complement the mitomycin C (MMC)-sensitive phenotype of FA-A cells. The overlapping genomic organization between Zfp276 and Fanca may have relevance to the disease phenotype of FA. Copyright 2000 Academic Press.
Phenotypic and pathologic evaluation of the myd mouse. A candidate model for facioscapulohumeral dystrophy
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Mathews, K.D.; Rapisarda, D.; Bailey, H.L. [Univ. of Iowa College of Medicine, Iowa City, IA (United States)] [and others
Facioscapulohumeral dystrophy (FSHD) is an autosomal dominant disease of unknown pathogenesis which is characterized by weakness of the face and shoulder girdle. It is associated with a sensorineural hearing loss which may be subclinical. FSHD has been mapped to the distalmost portion of 4q35, although the gene has not yet been identified. Distal 4q has homology with a region of mouse chromosome 8 to which a mouse mutant, myodystrophy (myd), has been mapped. Muscle from homozygotes for the myd mutation appears dystrophic, showing degenerating and regenerating fibers, inflammatory infiltrates, central nuclei, and variation in fiber size. Brainstem auditory evoked potentials reveal a sensorineural hearing loss in myd homozygotes. Based on the homologous genetic map locations, and the phenotypic syndrome of dystrophic muscle with sensorineural hearing loss, we suggest that myd represents an animal model for the human disease FSHD. 28 refs., 4 figs.
Qualitative analysis of mouse specific-locus mutations: information on genetic organization, gene expression, and the chromosomal nature of induced lesions
International Nuclear Information System (INIS)
Russell, L.B.
Analysis of mouse specific-locus (SL) mutations at three loci has identified over 33 distinct complementation groups - most of which are probably overlapping deficiencies - and 13 to 14 new functional units. The complementation maps that have been generated for the d-se and c regions include numerous vital functions; however, some of the genes in these regions are non-vital. At such loci, hypomorphic mutants must represent intragenic alterations, and some viable nulls could conceivably be intragenic lesions also. Analysis of SL mutations has provided information on genetic expression. Homozygous deficiencies can be completely viable or can kill at any one of a range of developmental stages. Heterozygonus deficiencies of up to 6 cM or more in genetic length have been recovered and propagated. The time of death of homozygous and the degree of inviability of heterozygous deficiencies are related more to specific content of the missing segment than to its length. Combinations of deficiencies with x-autosome translocations that inactivate the homologous region in a mosaic fashion have shown that organismic lethals are not necessarily cell lethal. The spectrum of mutations induced depends on the nature of the mutagen and the type of germ cell exposed. Radiation of spermatogonia produces intragenic as well as null mutations. Spontaneous mutations have an admixture of types not present in populations of mutations induced in germ cells, and this raises doubts concerning the accuracy of doubling-dose calculations in genetic risk estimation. The analysis of SL mutations has yielded genetic tools for the construction of detailed gene-dosage series, cis-trans comparisons, the mapping of known genes and identification of new genes, genetic rescue of various types, and the identification and isolation of DNA sequences
Identification of the UBP1 locus as a critical blood pressure determinant using a combination of mouse and human genetics
DEFF Research Database (Denmark)
Koutnikova, Hana; Laakso, Markku; Lu, Lu
complementarities of mouse and human genetic approaches, identifies the UBP1 locus as a critical blood pressure determinant. UBP1 plays a role in cholesterol and steroid metabolism via the transcriptional activation of CYP11A, the rate-limiting enzyme in pregnenolone and aldosterone biosynthesis. We suggest......Hypertension is a major health problem of largely unknown genetic origins. To identify new genes responsible for hypertension, genetic analysis of recombinant inbred strains of mice followed by human association studies might prove powerful and was exploited in our current study. Using a set of 27...... recombinant BXD strains of mice we identified a quantitative trait locus (QTL) for blood pressure (BP) on distal chromosome 9. The association analysis of markers encompassing the syntenic region on human chromosome 3 gave in an additive genetic model the strongest association for rs17030583 C/T and rs2291897...
Paternal isodisomy of chromosome 6 in association with a maternal supernumerary marker chromosome (6)
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James, R.S.; Crolla, J.A.; Sitch, F.L. [Salisbury District Hospital, Wiltshire (United Kingdom)] [and others
Uniparental disomy may arise by a number of different mechanisms of aneuploidy correction. A population that has been identified as being at increased risk of aneuploidy are those individuals bearing supernumerary marker chromosomes (SMCs). There have been a number of cases reported of trisomy 21 in association with bi-satellited marker chromosomes have described two individuals with small inv dup (15) markers. One had paternal isodisomy of chromosome 15 and Angelman syndrome. The other had maternal heterodisomy (15) and Prader-Willi syndrome. At the Wessex Regional Genetics Laboratory we have conducted a search for uniparental disomy of the normal homologues of the chromosomes from which SMCs originated. Our study population consists of 39 probands with SMCs originating from a number of different autosomes, including 17 with SMCs of chromosome 15 origin. Using PCR amplification of microsatellite repeat sequences located distal to the regions included in the SMCs we have determined the parental origin of the two normal homologues in each case. We have identified paternal isodisomy of chromosome 6 in a female child with a supernumerary marker ring chromosome 6 in approximately 70% of peripheral blood lymphocytes. The marker was found to be of maternal origin. This is the second case of paternal isodisomy of chromosome 6 to be reported, and the first in association with a SMC resulting in a partial trisomy for a portion of the short arm of chromosome 6. In spite of this, the patient appears to be functioning appropriately for her age.
Distal corporoplasty for distal cylinders extrusion after penile prosthesis implantation.
Carrino, Maurizio; Chiancone, Francesco; Battaglia, Gaetano; Pucci, Luigi; Fedelini, Paolo
Distal extrusion of cylinders is a potential complication of the penile prosthesis implantation. Several methods have been proposed for repairing a distal penile erosion. We present our preliminary experience in "Distal corporoplasty" technique. We enrolled 18 consecutive patients whose underwent a distal corporoplasty with simultaneous reimplantation of an "AMS 700 inflatable penile prosthesis (LGX)" from January 2013 to November 2015 at our hospital. All procedures were performed by a single surgical team. Intraoperative and postoperative complications have been classified and reported according to Satava6 and Clavien-Dindo (CD) system.7 Mean values with standard deviations (±SD) were computed and reported for all items. Mean age of the patients was 53.61 (±11.90) years. Mean body max index (BMI) was 24.22 (±2.51). Mean operative time was 85.2 (±13.1) minutes. Blood losses were minimal. No intraoperative complications are reported according to Satava classification. Four out of 18 patients (22.22%) experienced postoperative complications according to CD system. All patients had sexual intercourse for the first time postsurgery after a mean of 59.11 ± 2.08 days. Mean follow-up was 22.11 (±9.95). Distal extrusion of cylinders is a potential complication of the penile prosthesis implantation. Distal corporoplasty was first described by Mulcahy. He reported a series of 14 patients with a follow-up of about 2 years with optimal functional outcomes. Moreover, distal corporoplasty resulted in shorter operative time, better function, less pain, and fewer recurrences than Gortex windsock repair.10 In our experience, distal corporoplasty is a simple and safe procedure in the treatment of distal cylinders extrusion when the prosthetic material is not exposed to the exterior.
Meiotic synapsis of homogeneously staining regions (HSRs) in chromosome 1 of Mus musculus.
Winking, H; Reuter, C; Traut, W
About 50 copies of a long-range repeat DNA family with a repeat size of roughly 100 kb and with sequence homology to mRNAs are clustered in the G-light band D of chromosome 1 of the house mouse, Mus musculus. We studied amplified versions of the cluster which are found in many wild populations of M. musculus. They are cytogenetically conspicuous as one or two C-band positive homogeneously staining regions (single- and double band HSRs) which increase the mitotic length of chromosome 1. The double band HSR was phylogenetically derived from a single band HSR by a paracentric inversion. In homozygous condition, such HSRs contribute, albeit not as much as expected from their mitotic length, to the synaptonemal complex (SC) length of chromosome 1. In HSR heterozygous animals an elongation of the SCs was not noticeable. In single band HSR heterozygous males, synapsis proceeds regularly and continuously from the distal telomere towards the centromeric end without forming buckles. Thus, the single band HSR has no adverse effect on pairing. The same straight pairing behaviour was found in the majority of double band HSR heterozygous spermatocytes. This shows that extensive nonhomologous pairing can take place in the earliest phase of synapsis. Synapsis was discontinuous, leaving the central part of the bivalent 1 asynapsed, in only 14.3% of double band HSR heterozygous cells. In such cells the chromosome 1 SC is completed at a later stage of meiosis. The delay is presumably an effect of the inversion that includes one HSR band and the segment between the two HSR bands.
A 45 X male patient with 7q distal deletion and rearrangement with SRY gene translocation: a case report.
Bilen, S; Okten, A; Karaguzel, G; Ikbal, M; Aslan, Y
Here we present a male newborn with multiple congenital anomalies who also has an extremely rare form of testicular disorder of sex development (DSD). His karyotype was 45X, without any mosaicism. SRY gene was positive by polymerase chain reaction (PCR), and rearranged on distal part of the 7th chromosome by fluorescence in situ hybridization (FISH) analysis. SRY, normally located on the Y chromosome, is the most important gene that plays a role in the development of male sex. SRY gen may be translocated onto another chromosome, mostly X chromosome in the XX testicular DSD. On the other hand very few cases of 45 X testicular DSD were published to date. Other clinical manifestations of our patient were compatible with distal 7 q deletion syndrome. To the best of our knowledge this is the first case of 45 X testicular DSD with SRY gene rearranged on the 7th autosomal chromosome.
Reverse Distal Transverse Palmar Arch in Distal Digital Replantation.
Wei, Ching-Yueh; Orozco, Oscar; Vinagre, Gustavo; Shafarenko, Mark
Refinements in microsurgery have made distal finger replantation an established technique with high success rates and good functional and aesthetic outcomes. However, it still represents a technically demanding procedure due to the small vessel caliber and frequent lack of vessel length, requiring the use of interpositional venous grafts in some instances. We describe a new technique for anastomosis in fingertip replantation, whereby the need for venous grafts is eliminated. Applying the reverse distal transverse palmar arch technique, 11 cases of distal digital replantation were performed between January 2011 and July 2016. The described procedure was used for arterial anastomosis in 10 cases and arteriovenous shunting for venous drainage in 1 case. A retrospective case review was conducted. The technical description and clinical outcome evaluations are presented. Ten of the 11 replanted digits survived, corresponding to an overall success rate of 91%. One replant failed due to venous insufficiency. Blood transfusions were not required for any of the patients. Follow-up (range, 1.5-5 months) revealed near-normal range of motion and good aesthetic results. All of the replanted digits developed protective sensation. The average length of hospital admission was 5 days. All patients were satisfied with the results and were able to return to their previous work. The use of the reverse distal transverse palmar arch is a novel and reliable technique in distal digital replantation when an increase in vessel length is required, allowing for a tension-free arterial repair without the need for vein grafts.
The distal region of 11p13 and associated genetic diseases
Mannens, M.; Hoovers, J. M.; Bleeker-Wagemakers, E. M.; Redeker, E.; Bliek, J.; Overbeeke-Melkert, M.; Saunders, G.; Williams, B.; van Heyningen, V.; Junien, C.
The distal region of human chromosome band 11p13 is believed to contain a cluster of genes involved in the development of the eye, kidney, urogenital tract, and possibly the nervous system. Genetic abnormalities of this region can lead to Wilms tumor, aniridia, urogenital abnormalities, and mental
Traumatic Distal Ulnar Artery Thrombosis
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Ahmet A. Karaarslan
Full Text Available This paper is about a posttraumatic distal ulnar artery thrombosis case that has occurred after a single blunt trauma. The ulnar artery thrombosis because of chronic trauma is a frequent condition (hypothenar hammer syndrome but an ulnar artery thrombosis because of a single direct blunt trauma is rare. Our patient who has been affected by a single blunt trauma to his hand and developed ulnar artery thrombosis has been treated by resection of the thrombosed ulnar artery segment. This report shows that a single blunt trauma can cause distal ulnar artery thrombosis in the hand and it can be treated merely by thrombosed segment resection in suitable cases.
Evaluation of Lama5 as a candidate for the mouse ragged (Ra) mutation
DEFF Research Database (Denmark)
Durkin, M E; Albrechtsen, R; Chambers, D M
The laminin alpha5 chain is a component of the basement membranes of many developing and adult tissues. The mouse laminin alpha5 chain gene (Lama5) has been mapped close to the locus of the semidominant ragged (Ra) mutation on distal chromosome 2. The cause of the Ra mutation, which is usually...... lethal in the homozygous state, has not been determined. We have investigated whether a defect in Lama5 is responsible for the ragged mutation, using the RaJ strain. No differences in the level of the laminin alpha5 chain transcript were found in placental RNA from homozygous RaJ mutant embryos compared...... to normal littermates. Antiserum raised against a recombinant laminin alpha5 chain polypeptide stained the basement membranes of both normal and homozygous mutant embryos to a similar extent. More precise mapping of Lama5 on an interspecific Ra backcross indicated that Lama5 is proximal to the Ra locus...
Chromosomal localization of the human diazepam binding inhibitor gene
International Nuclear Information System (INIS)
DeBernardi, M.A.; Crowe, R.R.; Mocchetti, I.; Shows, T.B.; Eddy, R.L.; Costa, E.
The authors have used in situ chromosome hybridization and human-mouse somatic cell hybrids to map the gene(s) for human diazepam binding inhibitor (DBI), an endogenous putative modulator of the γ-aminobutyric acid receptor acting at the allosteric regulatory center of this receptor that includes the benzodiazepine recognition site. In 784 chromosome spreads hybridized with human DBI cDNA, the distribution of 1,476 labeled sites revealed a significant clustering of autoradiographic grains (11.3% of total label) on the long arm of chromosome 2 (2q). Furthermore, 63.5% of the grains found on 2q were located on 2q12-21, suggesting regional mapping of DBI gene(s) to this segment. Secondary hybridization signals were frequently observed on other chromosomes and they were statistically significant mainly for chromosomes 5, 6, 11, and 14. In addition, DNA from 32 human-mouse cell hybrids was digested with BamHI and probed with human DBI cDNA. A 3.5-kilobase band, which probably represents the human DBI gene, was assigned to chromosome 2. Four higher molecular weight bands, also detected in BamHI digests, could not be unequivocally assigned. A chromosome 2 location was excluded for the 27-, 13-, and 10-kilobase bands. These results assign a human DBI gene to chromosome 2 (2q12-21) and indicate that three of the four homologous sequences detected by the human DBI probe are located on three other chromosomes
X-ray- and mitomycin C (MMC)-induced chromosome aberrations in spermiogenic germ cells and the repair capacity of mouse eggs for the X-ray and MMC damage
International Nuclear Information System (INIS)
Matsuda, Yoichi; Utsugi-Takeuchi, Toyoko; Tobari, Izuo; Seki, Naohiko; Chiba Univ.
Chromosome aberrations induced at the first-cleavage metaphase of eggs fertilized with sperm recovered from spermiogenic cells which had been X-irradiated and treated with mitomycin C (MMC) at various stages were observed using in vitro fertilization and embryo culture technique. Furthermore, the repair capacity of the fertilized eggs for X-ray- and MMC-induced DNA damage which was induced in the spermiogenic cells and retained in the sperm until fertilization was investigated by analysis of the potentiation effects of 2 repair inhibitors, 3-aminobenzamide (3AB) and caffeine on the yield of chromosome aberrations. The frequency of chromosome aberrations observed in the eggs fertilized with sperm recovered from speratozoa to late spermatid stage (0-8 days after X-irradiation). The induced chromosome aberrations followed by chromosome exchange through all the spermiogenic stages. The results suggest that the large amount of DNA lesions induced in spermiogenic cells by X-rays and MMC persist as reparable damage until sperm maturation and are effectively repaired in the cytoplasm of the fertilized eggs. (author). 29 refs.; 2 figs.; 2 tabs
Distal protection in cardiovascular medicine: current status.
Ali, Onn Akbar; Bhindi, Ravinay; McMahon, Aisling C; Brieger, David; Kritharides, Leonard; Lowe, Harry C
Iatrogenic and spontaneous downstream microembolization of atheromatous material is increasingly recognized as a source of cardiovascular morbidity and mortality. Devising ways of reducing this distal embolization using a variety of mechanical means--distal protection--is currently under intense and diverse investigation. This review therefore summarizes the present status of distal protection. It examines the problem of distal embolization, describes the available distal protection devices, reviews those areas of cardiovascular medicine where distal protection devices are being investigated, and discusses potential future developments.
Genome-wide detection of chromosomal rearrangements, indels, and mutations in circular chromosomes by short read sequencing
DEFF Research Database (Denmark)
Skovgaard, Ole; Bak, Mads; Løbner-Olesen, Anders
a combination of WGS and genome copy number analysis, for the identification of mutations that suppress the growth deficiency imposed by excessive initiations from the Escherichia coli origin of replication, oriC. The E. coli chromosome, like the majority of bacterial chromosomes, is circular, and DNA...... replication is initiated by assembling two replication complexes at the origin, oriC. These complexes then replicate the chromosome bidirectionally toward the terminus, ter. In a population of growing cells, this results in a copy number gradient, so that origin-proximal sequences are more frequent than...... origin-distal sequences. Major rearrangements in the chromosome are, therefore, readily identified by changes in copy number, i.e., certain sequences become over- or under-represented. Of the eight mutations analyzed in detail here, six were found to affect a single gene only, one was a large chromosomal...
Genetic maps of polymorphic DNA loci on rat chromosome 1
Energy Technology Data Exchange (ETDEWEB)
Ding, Yan-Ping; Remmers, E.F.; Longman, R.E. [National Institutes of Health, Bethesda, MD (United States)] [and others
Genetic linkage maps of loci defined by polymorphic DNA markers on rat chromosome 1 were constructed by genotyping F2 progeny of F344/N x LEW/N, BN/SsN x LEW/N, and DA/Bkl x F344/Hsd inbred rat strains. In total, 43 markers were mapped, of which 3 were restriction fragment length polymorphisms and the others were simple sequence length polymorphisms. Nineteen of these markers were associated with genes. Six markers for five genes, {gamma}-aminobutyric acid receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}3 (Gabrb3), syntaxin 2 (Stx2), adrenergic receptor {beta}1 (Adrb1), carcinoembryonic antigen gene family member 1 (Cgm1), and lipogenic protein S14 (Lpgp), and 20 anonymous loci were not previously reported. Thirteen gene loci (Myl2, Aldoa, Tnt, Igf2, Prkcg, Cgm4, Calm3, Cgm3, Psbp1, Sa, Hbb, Ins1, and Tcp1) were previously mapped. Comparative mapping analysis indicated that the large portion of rat chromosome 1 is homologous to mouse chromosome 7, although the homologous to mouse chromosome 7, although the homologs of two rat genes are located on mouse chromosomes 17 and 19. Homologs of the rat chromosome 1 genes that we mapped are located on human chromosomes 6, 10, 11, 12, 15, 16, and 19. 38 refs., 1 fig., 3 tabs.
Fetal chromosome analysis: screening for chromosome disease?
DEFF Research Database (Denmark)
Philip, J; Tabor, Ann; Bang, J
The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...... A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were compared...... to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25-34 years of age, in whom all heritable diseases were excluded (group C). The risk of unbalanced...
Conserved chromosomal positions of dual domains of the ets protooncogene in cats, mice, and humans
International Nuclear Information System (INIS)
Watson, D.K.; McWilliams-Smith, M.J.; Kozak, C.
The mammalian protooncogene homologue of the avian v-ets sequence from the E26 retrovirus consists of two sequentially distinct domains located on different chromosomes. Using somatic cell hybrid panels, the authors have mapped the mammalian homologue of the 5' v-ets-domain to chromosome 11 (ETS1) in man, to chromosome 9 (ets-1) in mouse, and to chromosome D1 (ETS1) in the domestic cat. The mammalian homologue of the 3' v-ets domain was similarly mapped to human chromosome 21 (ETS2), to mouse chromosome 16 (Ets-2), and to feline chromosome C2 (ETS2). Both protooncogenes fell in syntenic groups of homologous linked loci that were conserved among the three species. The occurrence of two distinct functional protooncogenes and their conservation of linkage positions in the three mammalian orders indicate that these two genes have been separate since before the evolutionary divergence of mammals
Molecular cytogenetic analysis and clinical manifestations of a case with de novo mosaic ring chromosome 7
Directory of Open Access Journals (Sweden)
Fang Jye-Siung
Full Text Available Abstract Aim Clinical and molecular cytogenetic investigations of a newborn girl exhibiting facial dysmorphism with developmental delay. Methods Phenotypic evaluation was first applied to examine the proband's developmental status. Computed tomography and colour transcranial Doppler were used then to investigate her brain structure and function. Subsequently, chromosomal abnormalities were examined by karyotyping and fluorescent in situ hybridization was performed to investigate size of fragments lost at the two distal ends of the ring chromosome 7. In addition, multicolour banding was applied to rule out structural rearrangement occurs in between the ring chromosome 7. Results The proband was born with mosaic supernumerary ring chromosome 7, without a normal karyotype detected in the peripheral blood lymphocytes. The distal arm of chromosome 7p (at least 255 kb from the telomere was part of an extra ring chromosome 7. In addition, the distal arm of 7q, at least 8 kb from the telomere, was missing. There was no other chromosomal rearrangement detected by multicolour banding. Interpretation This is the 19th reported case of complete ring chromosome 7 mosaicism and the first survived case with mosaic supernumerary ring 7 without a normal karyotype detected in the peripheral lymphocytes.
Chromosome painting in plants.
Schubert, I.; Fransz, P.F.; Fuchs, J.; Jong, de J.H.
The current 'state-of-art' as to chromosome painting in plants is reviewed. We define different situations described as painting so far: i) Genomic in situ hybridisation (GISH) with total genomic DNA to distinguish alien chromosomes on the basis of divergent dispersed repeats, ii) 'Chromosomal in
Spleen-preserving distal pancreatectomy in trauma.
Schellenberg, Morgan; Inaba, Kenji; Cheng, Vincent; Bardes, James M; Lam, Lydia; Benjamin, Elizabeth; Matsushima, Kazuhide; Demetriades, Demetrios
Traumatic injuries to the distal pancreas are infrequent. Universally accepted recommendations about the need for routine splenectomy with distal pancreatectomy do not exist. The aims of this study were to compare outcomes after distal pancreatectomy and splenectomy versus spleen-preserving distal pancreatectomy, and to define the appropriate patient population for splenic preservation. All patients who underwent distal pancreatectomy (January 1, 2007, to December 31, 2014) were identified from the National Trauma Data Bank. Patients with concomitant splenic injury and those who underwent partial splenectomy were excluded. Demographics, clinical data, procedures, and outcomes were collected. Study groups were defined by surgical procedure: distal pancreatectomy and splenectomy versus spleen-preserving distal pancreatectomy. Baseline characteristics between groups were compared with univariate analysis. Multivariate analysis was performed with logistic and linear regression to examine differences in outcomes. Over the 8-year study period, 2,223 patients underwent distal pancreatectomy. After excluding 1,381 patients with concomitant splenic injury (62%) and 8 (pancreatectomy and splenectomy, those who underwent spleen-preserving distal pancreatectomy were younger (p pancreatectomy (p = 0.017). Complications, mortality, and intensive care unit LOS were not significantly different. In young patients after blunt trauma who are not severely injured, a spleen-preserving distal pancreatectomy should be considered to allow for conservation of splenic function and a shorter hospital LOS. In all other patients, the surgeon should not hesitate to remove the spleen with the distal pancreas. Therapy, level IV.
Bands and chromosome arrangement in interphase nuclei
International Nuclear Information System (INIS)
Bianchi, N.O.; Bianchi, M.A.; Matayoshi, T.
Chromosomes from the vole mouse Akodon dolores and from laboratory mouse showed the presence of G-bands after 3 minutes digestion with trypsin and Giemsa stain. Simultaneously, 30- to 40% of the interphase nuclei exhibited a dark ring parallel to the nuclear contour and a radial array of the chromatin in the internal and external regions of the ring. The origin and meaning of this ring image was analyzed by combining progressive trypsinizations with other methods such as C-banding procedures, autoradiography with 3 HTdR, staining with quinacrine mustard and 33258 Hoechst fluorochromes. Moreover, the presence of the dark ring was also investigated in cells treated with actinomycin and in control cells not subjected to any treatment. The results obtained allowed to assume that in interphase nuclei the chromosomes have chromatin bridges which connect the dark G-bands and that these bridges are probably involved in maintaining an ordered architecture of the nucleus with fixed chromosome positions in regard to the nuclear envelope and in regard to other chromosomes. Trypsinization produces a disruption of the interphase chromatin arrangement and the subsequent appearance of a dark ring formed by the combination of constitutive heterochromatin and dark G-bands. (auth.)
Cultures of preimplantation mouse embryos
International Nuclear Information System (INIS)
Streffer, C.; Molls, M.
In the preimplantation mouse embryos the chromosomal damage develops through several postradiation cell cycles and mitoses. New chromosome aberrations are seen during the second and third postradiation mitoses. Also, more micronuclei appear during later postradiation interphases. This is in agreement with the assumption that unrepaired chromosomal radiation damage develops during the cell generation cycle to such a form (i.e. double-strand breaks in DNA) that chromosomal breaks occur. This proposition is strengthened by the observation that radiation-induced damage is more rapidly expressed after neutron exposure (first or second postradiation mitosis) than after exposure to X rays at the one- or two-cell stage. The preimplantation mouse embryo culture is an inviting system for additional studies at the molecular level, especially now that within the last few years more sensitive methods have been developed for study of DNA and protein structure, regulation, and synthesis. The results from these studies of cultures of preimplantation mouse embryos present a favorable case for the study of complex biological systems under very defined conditions in vitro for extrapolation to effects in vivo
Bloom syndrome and maternal uniparental disomy for chromosome 15
Energy Technology Data Exchange (ETDEWEB)
Woodage, T.; Prasad, M.; Trent, R.J.; Smith, A. (Children' s Hospital, Camperdown, New South Wales (New Zealand)); Dixon, J.W.; Romain, D.R.; Columbano-Green, L.M.; Selby, R.E. (Wellington Hospital (New Zealand)); Graham, D. (Waikato Hospital, Hamilton (New Zealand)); Rogan, P.K. (Pennsylvania State Univ., Hershey, PA (United States)) (and others)
Bloom syndrome (BS) is an autosomal recessive disorder characterized by increases in the frequency of sister-chromatid exchange and in the incidence of malignancy. Chromosome-transfer studies have shown the BS locus to map to chromosome 15q. This report describes a subject with features of both BS and Prader-Willi syndrome (PWS). Molecular analysis showed maternal uniparental disomy for chromosome 15. Meiotic recombination between the two disomic chromosomes 15 has resulted in heterodisomy for proximal 15q and isodisomy for distal 15q. In this individual BS is probably due to homozygosity for a gene that is telomeric to D15S95 (15q25), rather than to genetic imprinting, the mechanism responsible for the development of PWS. This report represents the first application of disomy analysis to the regional localization of a disease gene. This strategy promises to be useful in the genetic mapping of other uncommon autosomal recessive conditions. 37 refs., 3 figs., 2 tabs.
Distribution of X-ray induced chromosome rearrangement breaks along the polytene chromosomes of Anopheles messeae
International Nuclear Information System (INIS)
Pleshkova, G.N.
Distribution of chromosomal aberrations localization along polytene chromosomes (aoutosomes) of salivary glands of malarial mosquito. Anopheles messeae is presented. Induced aberrations in F 1 posterity from X-ray irradiated fecundated females are studied. Poipts of breaks of inversions and trapslocations are localized separately. There are no considerable dif-- ferences in the distribution character of two types of aberrations. Over the length of autosomes the breaks are more frequent in distal halves, their frequency in proximal parts anally in near centromeric regions of chromosomes is reduced. Concentration of breaks in certain ''hot points'' of the chromosomes is pointed out. Comparison of distribution of actual and expected frequencies of break points according to chi 2 criterion revealed highly fiducial discrepancies, testifying to uneven participation of different regions of chromosomes in aberration formation. Similarities and differences of the data obtained from analogous ones, demonstrated in Drosophila, as well as possible reasons for the distribution unevennes are discussed. On the basis of analysis of intrinsic and literature data a supposition is made that the ''hot points'' (break concentrations) can be considered as localizaion markers of intercalary heterochromatin
Chromosome survey for children of A-bomb survivors
International Nuclear Information System (INIS)
Awa, Akio
To investigate chromosomes from children of A-bomb survivors, cytogenetic survey has been started in 1967 by the ABCC and completed in 1985 by the succeeding RERF. This paper is designed to overview the cytogenetic survey and to discuss the cytogenetic effects of A-bomb radiation. A cohort of 16,298 children of A-bomb survivors, which were collected from mortality survey population in 1974, was enrolled in this survey and was divided into two groups: the proximally exposed group (n=8,322, whose parents exposed to estimated doses of 0.01 Gy or more within 2,000 m from the hypocenter) and the distally exposed group (n=7,976, those exposed to 0.005 Gy or less far from 2,500 m or not in the city). Three chromosomal aberrations were identified: sex chromosome aberrations consisting mainly of XYY, XXY, and mosaic; structural abnormality of autosomes consisting mainly of translocation and inversion; and trisomy of autosomes. Overall, the incidence of chromosomal aberrations was higher in the distally exposed group (6.39%) than the proximally exposed group (5.17%). According to the type of chromosomal aberrations, the incidences of both sex chromosomes and structural abnormality of autosomes were slightly higher in the distally exposed group (0.30% and 0.34%) than the proximally exposed group (0.23% and 0.28%). Trisomy of autosomes was identified in only one child in the proximally exposed group. These findings failed to demonstrate the rationale for the cytogenetic effects of A-bomb radiation; however, cytogenetic risk of radiation has not been denied completely. (N.K.)
X Chromosome Inactivation and Breast Cancer: Epigenetic Alteration in Tumor Initiation and Progression
National Research Council Canada - National Science Library
Panning, Barbara
We tested whether reactivation of the inactive X chromosome in the mouse mammary gland contributes to tumorigenesis in vivo and whether that reactivation of the inactive X can cooperate with the MYC...
Chromosomal organization of adrenergic receptor genes
International Nuclear Information System (INIS)
Yang-Feng, T.L.; Xue, Feiyu; Zhong, Wuwei; Cotecchia, S.; Frielle, T.; Caron, M.G.; Lefkowitz, R.J.; Francke, U.
The adrenergic receptors (ARs) (subtypes α 1 , α 2 , β 1 , and β 2 ) are a prototypic family of guanine nucleotide binding regulatory protein-coupled receptors that mediate the physiological effects of the hormone epinephrine and the neurotransmitter norepinephrine. The authors have previously assigned the genes for β 2 -and α 2 -AR to human chromosomes 5 and 10, respectively. By Southern analysis of somatic cell hybrids and in situ chromosomal hybridization, they have now mapped the α 1 -AR gene to chromosome 5q32→q34, the same position as β 2 -AR, and the β 1 -AR gene to chromosome 10q24→q26, the region where α 2 -AR, is located. In mouse, both α 2 -and β 1 -AR genes were assigned to chromosome 19, and the α 1 -AR locus was localized to chromosome 11. Pulsed field gel electrophoresis has shown that the α 1 -and β 2 -AR genes in humans are within 300 kilobases (kb) and the distance between the α 2 - and β 1 -AR genes is <225 kb. The proximity of these two pairs of AR genes and the sequence similarity that exists among all the ARs strongly suggest that they are evolutionarily related. Moreover, they likely arose from a common ancestral receptor gene and subsequently diverged through gene duplication and chromosomal duplication to perform their distinctive roles in mediation the physiological effects of catecholamines. The AR genes thus provide a paradigm for understanding the evolution of such structurally conserved yet functionally divergent families off receptor molecules
Chromosomal heterozygosity and fertility in house mice (Mus musculus domesticus) from Northern Italy.
Hauffe, H C; Searle, J B
Following the discovery of over 40 Robertsonian (Rb) races of Mus musculus domesticus in Europe and North Africa, the house mouse has been studied extensively as an ideal model to determine the chromosomal changes that may cause or accompany speciation. Current models of chromosomal speciation are based on the assumption that heterozygous individuals have a particularly low fertility, although recent studies indicate otherwise. Despite their importance, fertility estimates for the house mouse...
Chromosomal Evolution in Chiroptera.
Sotero-Caio, Cibele G; Baker, Robert J; Volleth, Marianne
Chiroptera is the second largest order among mammals, with over 1300 species in 21 extant families. The group is extremely diverse in several aspects of its natural history, including dietary strategies, ecology, behavior and morphology. Bat genomes show ample chromosome diversity (from 2n = 14 to 62). As with other mammalian orders, Chiroptera is characterized by clades with low, moderate and extreme chromosomal change. In this article, we will discuss trends of karyotypic evolution within distinct bat lineages (especially Phyllostomidae, Hipposideridae and Rhinolophidae), focusing on two perspectives: evolution of genome architecture, modes of chromosomal evolution, and the use of chromosome data to resolve taxonomic problems.
Chromosomal Evolution in Chiroptera
Directory of Open Access Journals (Sweden)
Cibele G. Sotero-Caio
Full Text Available Chiroptera is the second largest order among mammals, with over 1300 species in 21 extant families. The group is extremely diverse in several aspects of its natural history, including dietary strategies, ecology, behavior and morphology. Bat genomes show ample chromosome diversity (from 2n = 14 to 62. As with other mammalian orders, Chiroptera is characterized by clades with low, moderate and extreme chromosomal change. In this article, we will discuss trends of karyotypic evolution within distinct bat lineages (especially Phyllostomidae, Hipposideridae and Rhinolophidae, focusing on two perspectives: evolution of genome architecture, modes of chromosomal evolution, and the use of chromosome data to resolve taxonomic problems.
Increased chromosome radiosensitivity during pregnancy
International Nuclear Information System (INIS)
Ricoul, Michelle; Sabatier, Laure; Dutrillaux, Bernard
It was necessary to consider the risks of exposure of pregnant women, not only in relation to the child, but also in relation to their own hypersensitivity. We have demonstrated that pregnancy increases radiosensitivity of chromosome in the mouse at the end of gestation. This is of importance since it may have implications on radioprotection of pregnant women and give experimental guidelines to the problems of hypersensitivity to drugs and cancer aggravation during pregnancy. Blood obtained from women at various times of pregnancy was exposed to ionizing radiations. By comparison to non-pregnant women, an increase in chromosome breakage was observed in metaphases from lymphocytes, after short-term culture in the presence of the serum of the same donor. Immediately after delivery, this increase in radiosensitivity disappeared. In a prospective study, serial analyses showed a very strong correlation between the amount of pregnancy hormones, progesterone in particular, and the increase in radiosensitivity. Pregnant women may have an increased sensitivity to ionizing radiation during the second half of their pregnancy. This study provides the first evidence in human that radiosensitivity may vary in relation to physiological conditions
Progress towards construction of a total restriction fragment map of a human chromosome.
H. Vissing; F.G. Grosveld (Frank); E. Solomon; G. Moore; N. Lench; N. Shennan; R. Williamson
textabstractWe present an approach to the construction of an overlapping restriction fragment map of a single human chromosome. A genomic cosmid library genome was constructed from a mouse-human hybrid cell line containing chromosome 17 as its only human genetic component. Cosmids containing human
Human nucleolus organizers on nonhomologous chromosomes can share the same ribosomal gene variants.
Krystal, M; D'Eustachio, P; Ruddle, F H; Arnheim, N
The distributions of three human ribosomal gene polymorphisms among individual chromosomes containing nucleolus organizers were analyzed by using mouse--human hybrid cells. Different nucleolus organizers can contain the same variant, suggesting the occurrence of genetic exchanges among ribosomal gene clusters on nonhomologous chromosomes. Such exchanges appear to occur less frequently in mice. This difference is discussed in terms of the nucleolar organization and chromosomal location of ribosomal gene clusters in humans and mice. Images PMID:6272316
Report of the Fourth international workshop on human chromosome 18 mapping 1996
International Nuclear Information System (INIS)
Silverman, G.A.; Overhauser, J.; Gerken, S.; Aburomia, R.; O'Connell, P.; Krauter, K.S.; Detera-Wadleigh, S.D.; Yoshikawa, T.; Collins, A.R.; Geurts van Kessel, A.
The fourth international workshop on human chromosome 18 mapping was held in Boston, Massachusetts, USA on October 7-9, 1996. The workshop was attended by 34 participants from 7 countries. The goals of the workshop were to (1) generate integrated genetic and physical maps, (2) update the transcriptional map, (3) assess the syntenic relationships between human chromosome 18 and the mouse genome, and (4) establish a chromosome 18 web site
The putative oncogene Pim-1 in the mouse: its linkage and variation among t haplotypes.
Nadeau, J H; Phillips, S J
Pim-1, a putative oncogene involved in T-cell lymphomagenesis, was mapped between the pseudo-alpha globin gene Hba-4ps and the alpha-crystallin gene Crya-1 on mouse chromosome 17 and therefore within the t complex. Pim-1 restriction fragment variants were identified among t haplotypes. Analysis of restriction fragment sizes obtained with 12 endonucleases demonstrated that the Pim-1 genes in some t haplotypes were indistinguishable from the sizes for the Pim-1b allele in BALB/c inbred mice. There are now three genes, Pim-1, Crya-1 and H-2 I-E, that vary among independently derived t haplotypes and that have indistinguishable alleles in t haplotypes and inbred strains. These genes are closely linked within the distal inversion of the t complex. Because it is unlikely that these variants arose independently in t haplotypes and their wild-type homologues, we propose that an exchange of chromosomal segments, probably through double crossingover, was responsible for indistinguishable Pim-1 genes shared by certain t haplotypes and their wild-type homologues. There was, however, no apparent association between variant alleles of these three genes among t haplotypes as would be expected if a single exchange introduced these alleles into t haplotypes. If these variant alleles can be shown to be identical to the wild-type allele, then lack of association suggests that multiple exchanges have occurred during the evolution of the t complex.
Frequent Chromosome Aberrations Revealed by Molecular Cytogenetic Studies in Patients with Aniridia
Crolla, John A.; van Heyningen, Veronica
Seventy-seven patients with aniridia, referred for cytogenetic analysis predominantly to assess Wilms tumor risk, were studied by fluorescence in situ hybridization (FISH), through use of a panel of cosmids encompassing the aniridia-associated PAX6 gene, the Wilms tumor predisposition gene WT1, and flanking markers, in distal chromosome 11p13. Thirty patients were found to be chromosomally abnormal. Cytogenetically visible interstitial deletions involving 11p13 were found in 13 patients, 11 o...
Posttraumatic osteolysis of the distal clavicula end
International Nuclear Information System (INIS)
Hermanns, P.H.; Beeger, R.; Koetter, D.; Hamburg Univ.
Posttraumatic osteolysis of bone is rare. Its etiology is unknown. A case of posttraumatic osteolysis of the distal clavicle end is reported. Differentialdiagnostical and ethiological relations are discussed. The literature of posttraumatic osteolysis especially of distal clavicle osteolysis is reported. (orig.) [de
Contemporary Management of Primary Distal Urethral Cancer
Traboulsi, S.L.; Witjes, J.A.; Kassouf, W.
Primary urethral cancer is one of the rare urologic tumors. Distal urethral tumors are usually less advanced at diagnosis compared with proximal tumors and have a good prognosis if treated appropriately. Low-stage distal tumors can be managed successfully with a surgical approach in men or radiation
Discrimination of chromosome by autoradiography
International Nuclear Information System (INIS)
Masubuchi, Masanori
This paper describes discrimination of chromosome by autoradiography. In this method, the difference in DNA synthetic phase between each chromosome was used as a standard, and the used chromosome was in metaphase, as morphological characteristics were markedly in this phase. Cell cycle and autoradiography with 3 H-thymidine were also examined. In order to discriminate chromosome by autoradiography, it was effective to utilize the labelled pattern in late DNA synthetic phase, where asynchronous replication of chromosome appeared most obviously. DNA synthesis in chromosome was examined in each DNA synthetic phase by culturing the chromosome after the treatment with 3 H-thymidine and altering the time to prepare chromosome specimen. Discrimination of chromosome in plants and animals by autoradiography was also mentioned. It was noticed as a structural and functional discrimination of chromosome to observe amino acid uptake into chromosome protein and to utilize the difference in labelled pattern between the sites of chromosome. (K. Serizawa)
DEFF Research Database (Denmark)
Philip, J; Tabor, A; Bang, J
The aim of the study was to investigate the rationale of the current indications for fetal chromosome analysis. 5372 women had 5423 amniocentesis performed, this group constituting a consecutive sample at the chromosome laboratory, Rigshospitalet, Copenhagen from March 1973 to September 1980 (Group...... A + B). Pregnant women 35 years of age, women who previously had a chromosomally abnormal child, families with translocation carriers or other heritable chromosomal disease, families where the father was 50 years or more and women in families with a history of Down's syndrome (group A), were compared...... to women having amniocentesis, although considered not to have any increased risk of fetal chromosome abnormality (1390 pregnancies, group B). They were also compared with 750 consecutive pregnancies in women 25-34 years of age, in whom all heritable diseases were excluded (group C). The risk of unbalanced...
Characterization of the distal promoter of the human pyruvate carboxylase gene in pancreatic beta cells.
Directory of Open Access Journals (Sweden)
Ansaya Thonpho
Full Text Available Pyruvate carboxylase (PC is an enzyme that plays a crucial role in many biosynthetic pathways in various tissues including glucose-stimulated insulin secretion. In the present study, we identify promoter usage of the human PC gene in pancreatic beta cells. The data show that in the human, two alternative promoters, proximal and distal, are responsible for the production of multiple mRNA isoforms as in the rat and mouse. RT-PCR analysis performed with cDNA prepared from human liver and islets showed that the distal promoter, but not the proximal promoter, of the human PC gene is active in pancreatic beta cells. A 1108 bp fragment of the human PC distal promoter was cloned and analyzed. It contains no TATA box but possesses two CCAAT boxes, and other putative transcription factor binding sites, similar to those of the distal promoter of rat PC gene. To localize the positive regulatory region in the human PC distal promoter, 5'-truncated and the 25-bp and 15-bp internal deletion mutants of the human PC distal promoter were generated and used in transient transfections in INS-1 832/13 insulinoma and HEK293T (kidney cell lines. The results indicated that positions -340 to -315 of the human PC distal promoter serve as (an activator element(s for cell-specific transcription factor, while the CCAAT box at -71/-67, a binding site for nuclear factor Y (NF-Y, as well as a GC box at -54/-39 of the human PC distal promoter act as activator sequences for basal transcription.
Directory of Open Access Journals (Sweden)
Julio R Daviña
Full Text Available Chromosome numbers of nine subtropical woody species collected in Argentina and Paraguay are reported. The counts tor Coutarea hexandra (2n=52, Inga vera subsp. affinis 2n=26 (Fabaceae and Chorisia speciosa 2n=86 (Bombacaceae are reported for the first time. The chromosome number given for Inga semialata 2n=52 is a new cytotype different from the previously reported. Somatic chromosome numbers of the other taxa studied are: Sesbania punicea 2n=12, S. virgata 2n=12 and Pilocarpus pennatifolius 2n=44 from Argentina
The mating-type chromosome in the filamentous ascomycete Neurospora tetrasperma represents a model for early evolution of sex chromosomes.
Directory of Open Access Journals (Sweden)
Audrius Menkis
Full Text Available We combined gene divergence data, classical genetics, and phylogenetics to study the evolution of the mating-type chromosome in the filamentous ascomycete Neurospora tetrasperma. In this species, a large non-recombining region of the mating-type chromosome is associated with a unique fungal life cycle where self-fertility is enforced by maintenance of a constant state of heterokaryosis. Sequence divergence between alleles of 35 genes from the two single mating-type component strains (i.e. the homokaryotic mat A or mat a-strains, derived from one N. tetrasperma heterokaryon (mat A+mat a, was analyzed. By this approach we were able to identify the boundaries and size of the non-recombining region, and reveal insight into the history of recombination cessation. The non-recombining region covers almost 7 Mbp, over 75% of the chromosome, and we hypothesize that the evolution of the mating-type chromosome in this lineage involved two successive events. The first event was contemporaneous with the split of N. tetrasperma from a common ancestor with its outcrossing relative N. crassa and suppressed recombination over at least 6.6 Mbp, and the second was confined to a smaller region in which recombination ceased more recently. In spite of the early origin of the first "evolutionary stratum", genealogies of five genes from strains belonging to an additional N. tetrasperma lineage indicate independent initiations of suppressed recombination in different phylogenetic lineages. This study highlights the shared features between the sex chromosomes found in the animal and plant kingdoms and the fungal mating-type chromosome, despite fungi having no separate sexes. As is often found in sex chromosomes of plants and animals, recombination suppression of the mating-type chromosome of N. tetrasperma involved more than one evolutionary event, covers the majority of the mating-type chromosome and is flanked by distal regions with obligate crossovers.
10. international mouse genome conference
Energy Technology Data Exchange (ETDEWEB)
Meisler, M.H.
Ten years after hosting the First International Mammalian Genome Conference in Paris in 1986, Dr. Jean-Louis Guenet presided over the Tenth Conference at the Pasteur Institute, October 7--10, 1996. The 1986 conference was a satellite to the Human Gene Mapping Workshop and had approximately 50 attendees. The 1996 meeting was attended by 300 scientists from around the world. In the interim, the number of mapped loci in the mouse increased from 1,000 to over 20,000. This report contains a listing of the program and its participants, and two articles that review the meeting and the role of the laboratory mouse in the Human Genome project. More than 200 papers were presented at the conference covering the following topics: International mouse chromosome committee meetings; Mutant generation and identification; Physical and genetic maps; New technology and resources; Chromatin structure and gene regulation; Rate and hamster genetic maps; Informatics and databases; and Quantitative trait analysis.
Chromosomal abnormalities and autism
Directory of Open Access Journals (Sweden)
Farida El-Baz
Conclusion: Chromosomal abnormalities were not detected in the studied autistic children, and so the relation between the genetics and autism still needs further work up with different study methods and techniques.
Chromosome condensation and segmentation
International Nuclear Information System (INIS)
Viegas-Pequignot, E.M.
Some aspects of chromosome condensation in mammalians -humans especially- were studied by means of cytogenetic techniques of chromosome banding. Two further approaches were adopted: a study of normal condensation as early as prophase, and an analysis of chromosome segmentation induced by physical (temperature and γ-rays) or chemical agents (base analogues, antibiotics, ...) in order to show out the factors liable to affect condensation. Here 'segmentation' means an abnormal chromosome condensation appearing systematically and being reproducible. The study of normal condensation was made possible by the development of a technique based on cell synchronization by thymidine and giving prophasic and prometaphasic cells. Besides, the possibility of inducing R-banding segmentations on these cells by BrdU (5-bromodeoxyuridine) allowed a much finer analysis of karyotypes. Another technique was developed using 5-ACR (5-azacytidine), it allowed to induce a segmentation similar to the one obtained using BrdU and identify heterochromatic areas rich in G-C bases pairs [fr
Chromosomal Evolution in Chiroptera
Sotero-Caio, Cibele G.; Baker, Robert J.; Volleth, Marianne
Chiroptera is the second largest order among mammals, with over 1300 species in 21 extant families. The group is extremely diverse in several aspects of its natural history, including dietary strategies, ecology, behavior and morphology. Bat genomes show ample chromosome diversity (from 2n = 14 to 62). As with other mammalian orders, Chiroptera is characterized by clades with low, moderate and extreme chromosomal change. In this article, we will discuss trends of karyotypic evolution within d...
Evolutionary rate of a gene affected by chromosomal position.
Perry, J; Ashworth, A
Genes evolve at different rates depending on the strength of selective pressure to maintain their function. Chromosomal position can also have an influence [1] [2]. The pseudoautosomal region (PAR) of mammalian sex chromosomes is a small region of sequence identity that is the site of an obligatory pairing and recombination event between the X and Y chromosomes during male meiosis [3] [4] [5] [6]. During female meiosis, X chromosomes can pair and recombine along their entire length. Recombination in the PAR is therefore approximately 10 times greater in male meiosis compared with female meiosis [4] [5] [6]. The gene Fxy (also known as MID1 [7]) spans the pseudoautosomal boundary (PAB) in the laboratory mouse (Mus musculus domesticus, C57BL/6) such that the 5' three exons of the gene are located on the X chromosome but the seven exons encoding the carboxy-terminal two-thirds of the protein are located within the PAR and are therefore present on both the X and Y chromosomes [8]. In humans [7] [9], the rat, and the wild mouse species Mus spretus, the gene is entirely X-unique. Here, we report that the rate of sequence divergence of the 3' end of the Fxy gene is much higher (estimated at 170-fold higher for synonymous sites) when pseudoautosomal (present on both the X and Y chromosomes) than when X-unique. Thus, chromosomal position can directly affect the rate of evolution of a gene. This finding also provides support for the suggestion that regions of the genome with a high recombination frequency, such as the PAR, may have an intrinsically elevated rate of sequence divergence.
Y chromosome gr/gr deletions are a risk factor for low semen quality
Visser, L.; Westerveld, G. H.; Korver, C. M.; van Daalen, S. K. M.; Hovingh, S. E.; Rozen, S.; van der Veen, F.; Repping, S.
Subfertility affects one in eight couples. In up to 50% of cases, the male partner has low semen quality. Four Y chromosome deletions, i.e. Azoospermia factor a (AZFa), P5/proximal-P1 (AZFb), P5/distal-P1 and AZFc deletions, are established causes of low semen quality. Whether a recently identified
Conceptualizing distal drivers in land use competition
DEFF Research Database (Denmark)
Niewhöner, Jörg; Nielsen, Jonas Ø; Gasparri, Gasparri
This introductory chapter explores the notion of 'distal drivers' in land use competition. Research has moved beyond proximate causes of land cover and land use change to focus on the underlying drivers of these dynamics. We discuss the framework of telecoupling within human–environment systems...... as a first step to come to terms with the increasingly distal nature of driving forces behind land use practices. We then expand the notion of distal as mainly a measure of Euclidian space to include temporal, social, and institutional dimensions. This understanding of distal widens our analytical scope...... for the analysis of land use competition as a distributed process to consider the role of knowledge and power, technology, and different temporalities within a relational or systemic analysis of practices of land use competition. We conclude by pointing toward the historical and social contingency of land use...
Distal technologies and type 1 diabetes management.
Duke, Danny C; Barry, Samantha; Wagner, David V; Speight, Jane; Choudhary, Pratik; Harris, Michael A
Type 1 diabetes requires intensive self-management to avoid acute and long-term health complications. In the past two decades, substantial advances in technology have enabled more effective and convenient self-management of type 1 diabetes. Although proximal technologies (eg, insulin pumps, continuous glucose monitors, closed-loop and artificial pancreas systems) have been the subject of frequent systematic and narrative reviews, distal technologies have received scant attention. Distal technologies refer to electronic systems designed to provide a service remotely and include heterogeneous systems such as telehealth, mobile health applications, game-based support, social platforms, and patient portals. In this Review, we summarise the empirical literature to provide current information about the effectiveness of available distal technologies to improve type 1 diabetes management. We also discuss privacy, ethics, and regulatory considerations, issues of global adoption, knowledge gaps in distal technology, and recommendations for future directions. Copyright © 2018 Elsevier Ltd. All rights reserved.
Genetics Home Reference: distal arthrogryposis type 1
... 1 is a disorder characterized by joint deformities (contractures) that restrict movement in the hands and feet. ... distal arthrogryposis type 1 . However, researchers speculate that contractures may be related to problems with muscle contraction ...
A human DAZ transgene confers partial rescue of the mouse Dazl null phenotype
Slee, R.; Grimes, B.; Speed, R. M.; Taggart, M.; Maguire, S. M.; Ross, A.; McGill, N. I.; Saunders, P. T. K.; Cooke, H. J.
In a subset of infertile men, a spectrum of spermatogenic defects ranging from a complete absence of germ cells (sertoli cell only) to oligozoospermia is associated with microdeletions of the DAZ (deleted in azoospermia) gene cluster on human distal Yq. DAZ encodes a testis-specific protein with RNA-binding potential recently derived from a single-copy gene DAZL1 (DAZ-like) on chromosome 3. Y chromosomal DAZ homologues are confined to humans and higher primates. It remains unclear which function unique to higher primate spermatogenesis DAZ may serve, and the functional status of the gene recently has been questioned. To assess the extent of functional conservation we have tested the capacity of a human DAZ gene contained in a 225-kb yeast artificial chromosome to complement the sterile phenotype of the Dazl null mouse (Dazl−/−), which is characterized by severe germ-cell depletion and meiotic failure. Although Dazl−/− mice remained infertile when the DAZ transgene was introduced, histological examination revealed a partial and variable rescue of the mutant phenotype, manifest as a pronounced increase in the germ cell population of the seminiferous tubules and survival to the pachytene stage of meiosis. As well as constituting definitive proof of the spermatogenic role of the DAZ gene product, these findings confirm the high degree of functional conservation between the DAZ and DAZL1 genes, suggesting they may constitute a single target for contraceptive intervention and raising the possibility of therapeutic up-regulation of the DAZL1 gene in infertile men. PMID:10393944
Micromechanics of human mitotic chromosomes
International Nuclear Information System (INIS)
Sun, Mingxuan; Kawamura, Ryo; Marko, John F
Eukaryote cells dramatically reorganize their long chromosomal DNAs to facilitate their physical segregation during mitosis. The internal organization of folded mitotic chromosomes remains a basic mystery of cell biology; its understanding would likely shed light on how chromosomes are separated from one another as well as into chromosome structure between cell divisions. We report biophysical experiments on single mitotic chromosomes from human cells, where we combine micromanipulation, nano-Newton-scale force measurement and biochemical treatments to study chromosome connectivity and topology. Results are in accord with previous experiments on amphibian chromosomes and support the 'chromatin network' model of mitotic chromosome structure. Prospects for studies of chromosome-organizing proteins using siRNA expression knockdowns, as well as for differential studies of chromosomes with and without mutations associated with genetic diseases, are also discussed
Normal distal pulmonary vein anatomy
Directory of Open Access Journals (Sweden)
Wiesława Klimek-Piotrowska
Full Text Available Background. It is well known that the pulmonary veins (PVs, especially their myocardial sleeves play a critical role in the initiation and maintenance of atrial fibrillation. Understanding the PV anatomy is crucial for the safety and efficacy of all procedures performed on PVs. The aim of this study was to present normal distal PV anatomy and to create a juxtaposition of all PV ostium variants.Methods. A total of 130 randomly selected autopsied adult human hearts (Caucasian were examined. The number of PVs ostia was evaluated and their diameter was measured. The ostium-to-last-tributary distance and macroscopic presence of myocardial sleeves were also evaluated.Results. Five hundred forty-one PV ostia were identified. Four classical PV ostia patterns (two left and two right PVs were observed in 70.8% of all cases. The most common variant was the classical pattern with additional middle right PV (19.2%, followed by the common ostium for the left superior and the inferior PVs (4.44%. Mean diameters of PV ostia (for the classical pattern were: left superior = 13.8 ± 2.9 mm; left inferior = 13.3 ± 3.4 mm; right superior = 14.3 ± 2.9 mm; right inferior = 13.7 ± 3.3 mm. When present, the additional middle right PV ostium had the smallest PV ostium diameter in the heart (8.2 ± 4.1 mm. The mean ostium-to-last-tributary (closest to the atrium distances were: left superior = 15.1 ± 4.6 mm; left inferior = 13.5 ± 4.0 mm; right superior = 11.8 ± 4.0 mm; right inferior = 11.0 ± 3.7 mm. There were no statistically significant differences between sexes in ostia diameters and ostium-to-last-tributary distances.Conclusion. Only 71% of the cases have four standard pulmonary veins. The middle right pulmonary vein is present in almost 20% of patients. Presented data can provide useful information for the clinicians during interventional procedures or radiologic examinations of PVs.
Effect of x-rays on the somatic chromosomes of the exotic fish, Tilapia mossambica
Energy Technology Data Exchange (ETDEWEB)
Manna, G.K.; Som, R.C. (Kalyani Univ. (India). Dept. of Zoology)
Male and female T. mossambica were x-rayed with 100 r and the metaphase chromosome aberrations in their gill epithelia were studied at 13 different intervals against suitable control. The chromosomes of males appeared more radio-sensitive than those of females. Among the diploid complement of 44 chromosomes, the individual type aberrations were non-random in both sexes. The longest pair of chromosomes, taken as the marker pair, was found very highly radio-sensitive, while the remaining 21 pairs as non-markers were somewhat resistant to x-radiation when the observed and the expected numbers were subjected to statistical analysis. The break in the marker chromosome was also non-randomly distributed as the distal half had a significantly large number of breaks.
DEFF Research Database (Denmark)
Liu, L; Vachon, P H; Kuang, W
. To analyze the biological roles of adhalin, we cloned the mouse adhalin cDNA, raised peptide-specific antibodies to its cytoplasmic domain, and examined its expression and localization in vivo and in vitro. The mouse adhalin sequence was 80% identical to that of human, rabbit, and hamster. Adhalin...... was specifically expressed in striated muscle cells and their immediate precursors, and absent in many other cell types. Adhalin expression in embryonic mouse muscle was coincident with primary myogenesis. Its expression was found to be up-regulated at mRNA and protein levels during myogenic differentiation...
Vibrio chromosome-specific families
DEFF Research Database (Denmark)
Lukjancenko, Oksana; Ussery, David
We have compared chromosome-specific genes in a set of 18 finished Vibrio genomes, and, in addition, also calculated the pan- and core-genomes from a data set of more than 250 draft Vibrio genome sequences. These genomes come from 9 known species and 2 unknown species. Within the finished...... chromosomes, we find a core set of 1269 encoded protein families for chromosome 1, and a core of 252 encoded protein families for chromosome 2. Many of these core proteins are also found in the draft genomes (although which chromosome they are located on is unknown.) Of the chromosome specific core protein...... families, 1169 and 153 are uniquely found in chromosomes 1 and 2, respectively. Gene ontology (GO) terms for each of the protein families were determined, and the different sets for each chromosome were compared. A total of 363 different "Molecular Function" GO categories were found for chromosome 1...
Distal 4p microdeletion in a case of Wolf-Hirschhorn syndrome with congenital diaphragmatic hernia.
Casaccia, Germana; Mobili, Luisa; Braguglia, Annabella; Santoro, Francesco; Bagolan, Pietro
Wolf-Hirschhorn syndrome (WHS) is a well-known genetic condition characterized by typical facial anomalies, midline defects, skeletal anomalies, prenatal and postnatal growth retardation, hypotonia, mental retardation, and seizures. Affected patients with a microdeletion on distal 4p present a milder phenotype that lacks congenital malformations. WHS is rarely associated with congenital diaphragmatic hernia (CDH), and only 8 cases are reported in the literature. In almost all cases of CDH and WHS a large deletion of the short arm of chromosome 4 is present. A microdeletion of 2.6 Mb on distal 4p associated with CDH and multiple congenital malformations (i.e., cleft palate) is reported for the first time. Such a microdeletion should prompt a molecular study for WHS when in a fetus/newborn with CDH the association with cleft lip/palate and typical facial appearance (flat facial profile, hypertelorism) is found. Copyright 2006 Wiley-Liss, Inc.
Physical mapping of the split hand/split foot (SHSF) locus on chromosome 7 reveals a relationship between SHSF and the syndromic ectrodactylies
Energy Technology Data Exchange (ETDEWEB)
Poorkaj, P.; Nunes, M.E.; Geshuri, D. [Univ. of Washington, Seattle, WA (United States)] [and others
Split hand/split foot (also knows as ectrodactyly) is a human developmental malformation characterized by missing digits and claw-like extremities. An autosomal dominant form of this disorder has been mapped to 7q21.3-q22.1 on the basis of SHSF-associated chromosomal rearrangements: this locus has been designated SHFD1. We have constructed a physical map of the SHFD1 region that consists of contiguous yeast artificial chromosome clones and spans approximately 8 Mb. Somatic cell hybrid and fluorescent in situ hybridization analyses were used to define SHSF-associated chromosomal breakpoints in fourteen patients. A critical interval of about 1 Mb was established for SHFD1 by analysis of six patients with deletions. Translocation and inversion breakpoints in seven other patients were found to localize within a 500-700 kb interval within the critical region. Several candidate genes including DLX5 and DLX6 (members of the Drosophilia Distal-less homeobox-containing gene family) localize to this region. At least four of these genes are expressed in the developing mouse limb bud. Of particular interest is the observation that 8 of the 14 patients studied have syndromic ectrodactyly, which is characterized by the association of SHSF with a variety of other anomalies including cleft lip/palate, ectodermal dysplasia, and renal anomalies. Thus, these data implicate a single gene or cluster of genes at the SHFD1 locus in a wide range of developmental processes and serve to establish a molecular genetic relationship between simple SHSF and a broad group of human birth defects.
Electochemical detection of chromosome translocation
DEFF Research Database (Denmark)
Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli
Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... chromosomes that results in formation of derivative chromosomes with a mixed DNA sequence. The method currently used for their detection is Fluorescent In Situ Hybridization, which requires a use of expensive, fluorescently labeled probes that target the derivative chromosomes. We present here a double...... hybridization approach developed for label-free detection of the chromosome translocations. For specific translocation detection it is necessary to determine that the two DNA sequences forming a derivative chromosome are connected, which is achieved by two subsequent hybridization steps. The electrochemical...
Mutations and chromosomal aberrations
International Nuclear Information System (INIS)
Kihlman, B.A.
The genetic changes of mutations and chromosomal aberrations are discussed. The consequences of both depend not only on the type of genetic change produced but also on the type of cell that is affected and on the development stage of the organism. (C.F.)
Chromosomes, cancer and radiosensitivity
International Nuclear Information System (INIS)
Samouhos, E.
Some specific chromosomal abnormalities are associated with certain cancers. The earliest description of such a specific association is the one of the Philadelphia chromosome and myelogenous leukemia (1960). Other congenital karyotype abnormalities are associated with specific cancers. Examples of these are Down's syndrome with leukemia and Klinefelter's syndrome with male breast cancer. Genetic diseases of increased chromosome breakage, or of defective chromosome repair, are associated with greatly increased cancer incidence. Three such diseases have been recognized: 1) Fanconi's anemia, associated with leukemias and lymphomas, 2) Bloom's syndrome, associated with acute leukemias and lymphosarcoma, and 3) ataxia telangiectasia, associated with Hodgkin's disease, leukemia, and lymphosarcomas. Ten percent of individuals with ataxia telangiectasia will develop one of these neoplasms. Individuals with certain of these syndromes display an unusually high radiosensitivity. Radiation therapy for cancers has been fatal in patients who received as low as 3000 rad. This remarkable radiosensitivity has been quantitated in cell cultures from such cases. Evidence suggests that the apparent sensitivity may reflect subnormal ability to repair radiation damage. The rapid proliferation of information in this field stems from the interdigitation of many disciplines and specialties, including cytogenetics, cell biology, molecular biology, epidemiology, radiobiology, and several others. This paper is intended for clinicians; it presents a structured analytic scheme for correlating and classifying this multidisciplinary information as it becomes available
Indian Academy of Sciences (India)
Home; Journals; Resonance – Journal of Science Education; Volume 1; Issue 3. Know Your Chromosomes The Strong Holds of Family Trees. Vani Brahmachari. Series Article Volume 1 Issue 3 March 1996 pp 30-38. Fulltext. Click here to view fulltext PDF. Permanent link:
DEFF Research Database (Denmark)
Brandt, C A; Hertz, Jens Michael; Petersen, M B
A stillborn male child with anencephaly and multiple malformations was found to have the karyotype 46,XY,r(13) (p11q21.1). The breakpoint at 13q21.1, determined by high resolution banding, is the most proximal breakpoint ever reported in patients with ring chromosome 13. In situ hybridisation...
Distal splenorenal shunt with partial spleen resection
Directory of Open Access Journals (Sweden)
Gajin Predrag
Full Text Available Introduction: Hypersplenism is a common complication of portal hypertension. Cytopenia in hypersplenism is predominantly caused by splenomegaly. Distal splenorenal shunt (Warren with partial spleen resection is an original surgical technique that regulates cytopenia by reduction of the enlarged spleen. Objective. The aim of our study was to present the advantages of distal splenorenal shunt (Warren with partial spleen resection comparing morbidity and mortality in a group of patients treated by distal splenorenal shunt with partial spleen resection with a group of patients treated only by a distal splenorenal shunt. Method. From 1995 to 2003, 41 patients with portal hypertension were surgically treated due to hypersplenism and oesophageal varices. The first group consisted of 20 patients (11 male, mean age 42.3 years who were treated by distal splenorenal shunt with partial spleen resection. The second group consisted of 21 patients (13 male, mean age 49.4 years that were treated by distal splenorenal shunt only. All patients underwent endoscopy and assessment of oesophageal varices. The size of the spleen was evaluated by ultrasound, CT or by scintigraphy. Angiography was performed in all patients. The platelet and white blood cell count and haemoglobin level were registered. Postoperatively, we noted blood transfusion, complications and total hospital stay. Follow-up period was 12 months, with first checkup after one month. Results In the first group, only one patient had splenomegaly postoperatively (5%, while in the second group there were 13 patients with splenomegaly (68%. Before surgery, the mean platelet count in the first group was 51.6±18.3x109/l, to 118.6±25.4x109/l postoperatively. The mean platelet count in the second group was 67.6±22.8x109/l, to 87.8±32.1x109/l postoperatively. Concerning postoperative splenomegaly, statistically significant difference was noted between the first and the second group (p<0.05. Comparing the
Contemporary Management of Primary Distal Urethral Cancer.
Traboulsi, Samer L; Witjes, Johannes Alfred; Kassouf, Wassim
Primary urethral cancer is one of the rare urologic tumors. Distal urethral tumors are usually less advanced at diagnosis compared with proximal tumors and have a good prognosis if treated appropriately. Low-stage distal tumors can be managed successfully with a surgical approach in men or radiation therapy in women. There are no clear-cut indications for the choice of the most appropriate treatment modality. Organ-preserving modalities have shown effective and should be used whenever they do not compromise the oncological safety to decrease the physical and psychological trauma of dismemberment or loss of sexual/urinary function. Copyright © 2016 Elsevier Inc. All rights reserved.
Spontaneous distal rupture of the plantar fascia.
Gitto, Salvatore; Draghi, Ferdinando
Spontaneous ruptures of the plantar fascia are uncommon injuries. They typically occur at its calcaneal insertion and usually represent a complication of plantar fasciitis and local treatment with steroid injections. In contrast, distal ruptures commonly result from traumatic injuries. We describe the case of a spontaneous distal rupture of the plantar fascia in a 48-year-old woman with a low level of physical activity and no history of direct injury to the foot, plantar fasciitis, or steroid injections. © 2017 Wiley Periodicals, Inc.
Torsion of wandering spleen and distal pancreas
International Nuclear Information System (INIS)
Sheflin, J.R.; Lee, C.M.; Kretchmar, K.A.
Wandering spleen is the term applied to the condition in which a long pedicle allows the spleen to lie in an abnormal location. Torsion of a wandering spleen is an unusual cause of an acute abdomen and is rarely diagnosed preoperatively. Associated torsion of the distal pancreas is even more uncommon. The authors describe a patient with torsion of a wandering spleen and distal pancreas, who was correctly diagnosed, and define the merits of the imaging methods used. The initial examination should be 99 /sup m/Tc-sulfur colloid liner-spleen scanning
Radiosensitivity of mouse germ cells
International Nuclear Information System (INIS)
Matsuda, Yoichi; Takeuchi, Toyoko; Maemori, Mamiko; Seki, Naohiko; Tobari, Izuo
To estimate radiosensitivity of mouse germ cells the analysis of chromosome aberrations was performed at diakinesis-metaphase I of spermatocytes and first-cleavage metaphase of one-cell embryos after exposure to radiations at various stages of primary spermatocytes and spermatids. The result provided evidence that there are two major types of DNA damage in X-irradiated sperm : (1) short-lived DNA lesions ; the lesions are subject to repair inhibition by agents added in G 1 , and are converted into chromosome-type aberrations during G 1 , and (2) long-lived DNA lesions ; the lesions persist until S phase and repair of the lesions is inhibited by caffeine, hydroxyurea and arabinofuranosyl cytosine in G 2 . The characteristic of X-ray damage induced in spermiogenic stage and repair mechanism for the damage in the fertilized egg were discussed comparing with the results with two chemicals, methyl methanesulfonate (MMS) and mitomycin C (MMC). (J.P.N.)
IL-6 and mouse oocyte spindle.
Directory of Open Access Journals (Sweden)
Jashoman Banerjee
Full Text Available Interleukin 6 (IL-6 is considered a major indicator of the acute-phase inflammatory response. Endometriosis and pelvic inflammation, diseases that manifest elevated levels of IL-6, are commonly associated with higher infertility. However, the mechanistic link between elevated levels of IL-6 and poor oocyte quality is still unclear. In this work, we explored the direct role of this cytokine as a possible mediator for impaired oocyte spindle and chromosomal structure, which is a critical hurdle in the management of infertility. Metaphase-II mouse oocytes were exposed to recombinant mouse IL-6 (50, 100 and 200 ng/mL for 30 minutes and subjected to indirect immunofluorescent staining to identify alterations in the microtubule and chromosomal alignment compared to untreated controls. The deterioration in microtubule and chromosomal alignment were evaluated utilizing both fluorescence and confocal microscopy, and were quantitated with a previously reported scoring system. Our results showed that IL-6 caused a dose-dependent deterioration in microtubule and chromosomal alignment in the treated oocytes as compared to the untreated group. Indeed, IL-6 at a concentration as low as 50 ng/mL caused deterioration in the spindle structure in 60% of the oocytes, which increased significantly (P<0.0001 as IL-6 concentration was increased. In conclusion, elevated levels of IL-6 associated with endometriosis and pelvic inflammation may reduce the fertilizing capacity of human oocyte through a mechanism that involves impairment of the microtubule and chromosomal structure.
Telomere dysfunction and chromosome instability
Energy Technology Data Exchange (ETDEWEB)
Murnane, John P., E-mail: email@example.com [Department of Radiation Oncology, University of California San Francisco, 2340 Sutter Street, San Francisco, CA 94143-1331 (United States)
The ends of chromosomes are composed of a short repeat sequence and associated proteins that together form a cap, called a telomere, that keeps the ends from appearing as double-strand breaks (DSBs) and prevents chromosome fusion. The loss of telomeric repeat sequences or deficiencies in telomeric proteins can result in chromosome fusion and lead to chromosome instability. The similarity between chromosome rearrangements resulting from telomere loss and those found in cancer cells implicates telomere loss as an important mechanism for the chromosome instability contributing to human cancer. Telomere loss in cancer cells can occur through gradual shortening due to insufficient telomerase, the protein that maintains telomeres. However, cancer cells often have a high rate of spontaneous telomere loss despite the expression of telomerase, which has been proposed to result from a combination of oncogene-mediated replication stress and a deficiency in DSB repair in telomeric regions. Chromosome fusion in mammalian cells primarily involves nonhomologous end joining (NHEJ), which is the major form of DSB repair. Chromosome fusion initiates chromosome instability involving breakage-fusion-bridge (B/F/B) cycles, in which dicentric chromosomes form bridges and break as the cell attempts to divide, repeating the process in subsequent cell cycles. Fusion between sister chromatids results in large inverted repeats on the end of the chromosome, which amplify further following additional B/F/B cycles. B/F/B cycles continue until the chromosome acquires a new telomere, most often by translocation of the end of another chromosome. The instability is not confined to a chromosome that loses its telomere, because the instability is transferred to the chromosome donating a translocation. Moreover, the amplified regions are unstable and form extrachromosomal DNA that can reintegrate at new locations. Knowledge concerning the factors promoting telomere loss and its consequences is
Homologous alpha satellite sequences on human acrocentric chromosomes with selectivity for chromosomes 13, 14, and 21: implications for recombination between nonhomologues and Robertsonian translocations
Energy Technology Data Exchange (ETDEWEB)
Choo, K H; Vissel, B; Brown, R; Filby, R G; Earle, E
The authors report a new subfamily of alpha satellite DNA (pTRA-2) which is found on all the human acrocentric chromosomes. The alphoid nature of the cloned DNA was established by partial sequencing. Southern analysis of restriction enzyme-digested DNA fragments from mouse/human hybrid cells containing only human chromosome 21 showed that the predominant higher-order repeating unit for pTRA-2 is a 3.9 kb structure. Analysis of a consensus in situ hybridization profile derived from 13 normal individuals revealed the localization of 73% of all centromeric autoradiographic grains over the five acrocentric chromosomes, with the following distribution: 20.4%, 21.5%, 17.1%, 7.3% and 6.5% on chromosomes 13, 14, 21, 15 and 22 respectively. An average of 1.4% of grains was found on the centromere of each of the remaining 19 nonacrocentric chromosomes. These results indicate the presence of a common subfamily of alpha satellite DNA on the five acrocentric chromosomes and suggest an evolutionary process consistent with recombination exchange of sequences between the nonhomologues. The results further suggests that such exchanges are more selective for chromosomes 13, 14 and 21 than for chromosomes 15 and 22. The possible role of centromeric alpha satellite DNA in the aetiology of 13q14q and 14q21q Robertsonian translocation involving the common and nonrandom association of chromosomes 13 and 14, and 14 and 21 is discussed.
Complementation of a DNA repair defect in xeroderma pigmentosum cells by transfer of human chromosome 9
International Nuclear Information System (INIS)
Kaur, G.P.; Athwal, R.S.
Complementation of the repair defect in xeroderma pigmentosum cells of complementation group A was achieved by the transfer of human chromosome 9. A set of mouse-human hybrid cell lines, each containing a single Ecogpt-marked human chromosome, was used as a source of donor chromosomes. Chromosome transfer to XPTG-1 cells, a hypoxanthine/guanine phosphoribosyltransferase-deficient mutant of simian virus 40-transformed complementation group A cells, was achieved by microcell fusion and selection for Ecogpt. Chromosome-transfer clones of XPTG-1 cells, each containing a different human donor chromosome, were analyzed for complementation of sensitivity to UV irradiation. Among all the clones, increased levels of resistance to UV was observed only in clones containing chromosome 9. Since our recipient cell line XPTG-1 is hypoxanthine/guanine phosphoribosyltransferase deficient, cultivation of Ecogpt+ clones in medium containing 6-thioguanine permits selection of cells for loss of the marker and, by inference, transferred chromosome 9. Clones isolated for growth in 6-thioguanine, which have lost the Ecogpt-marked chromosome, exhibited a UV-sensitive phenotype, confirming the presence of the repair gene(s) for complementation group A on chromosome 9
Endovascular treatment of ruptured distal posterior inferior ...
African Journals Online (AJOL)
Mar 1, 2014 ... there are lots of reports regarding the interventional therapy of the artery aneurysms (including proximal and distal), all of which are considered to be safe and effective. All the incidences of interventional-related complications are below 10% and there is no report of injury of lower cranial nerves [11, 12].
Urethral mobilization and advancement for distal hypospadias ...
African Journals Online (AJOL)
Background/purpose Despite the existence of numerous techniques for the repair of distal penile hypospadias, none of them is completely satisfactory. Advancing the urethra without mobilization for repair of glanular hypospadias has the advantage of avoiding a common problem occurring with other techniques: ...
Mechanisms of telomere loss and their consequences for chromosome instability
Energy Technology Data Exchange (ETDEWEB)
Muraki, Keiko; Nyhan, Kristine; Han, Limei; Murnane, John P., E-mail: email@example.com [Department of Radiation Oncology, University of California at San Francisco, San Francisco, CA (United States)
The ends of chromosomes in mammals, called telomeres, are composed of a 6-bp repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs) at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.
Mechanisms of telomere loss and their consequences for chromosome instability
International Nuclear Information System (INIS)
Muraki, Keiko; Nyhan, Kristine; Han, Limei; Murnane, John P.
The ends of chromosomes in mammals, called telomeres, are composed of a 6-bp repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs) at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.
Mechanisms of telomere loss and their consequences for chromosome instability
Directory of Open Access Journals (Sweden)
Keiko eMuraki
Full Text Available The ends of chromosomes in mammals, called telomeres, are composed of a 6 base pair repeat sequence, TTAGGG, which is added on by the enzyme telomerase. In combination with a protein complex called shelterin, these telomeric repeat sequences form a cap that protects the ends of chromosomes. Due to insufficient telomerase expression, telomeres shorten gradually with each cell division in human somatic cells, which limits the number of times they can divide. The extensive cell division involved in cancer cell progression therefore requires that cancer cells must acquire the ability to maintain telomeres, either through expression of telomerase, or through an alternative mechanism involving recombination. It is commonly thought that the source of many chromosome rearrangements in cancer cells is a result of the extensive telomere shortening that occurs prior to the expression of telomerase. However, despite the expression of telomerase, tumor cells can continue to show chromosome instability due to telomere loss. Dysfunctional telomeres in cancer cells can result from oncogene-induced replication stress, which results in double-strand breaks (DSBs at fragile sites, including telomeres. DSBs near telomeres are especially prone to chromosome rearrangements, because telomeric regions are deficient in DSB repair. The deficiency in DSB repair near telomeres is also an important mechanism for ionizing radiation-induced replicative senescence in normal human cells. In addition, DSBs near telomeres can result in chromosome instability in mouse embryonic stem cells, suggesting that telomere loss can contribute to heritable chromosome rearrangements. Consistent with this possibility, telomeric regions in humans are highly heterogeneous, and chromosome rearrangements near telomeres are commonly involved in human genetic disease. Understanding the mechanisms of telomere loss will therefore provide important insights into both human cancer and genetic disease.
Relative biological effectiveness (RBE) and distal edge effects of proton radiation on early damage in vivo
DEFF Research Database (Denmark)
Sørensen, Brita Singers; Bassler, Niels; Nielsen, Steffen
of the SOBP to behind the distal dose fall-off. Irradiations were performed with the same dose plan at all positions, corresponding to a dose of 31.25 Gy in the middle of the SOBP. Endpoint of the study was early skin damage of the foot, assessed by a mouse foot skin scoring system. RESULTS: The MDD50 values......, where LETd,z =1 was 3.3 keV/μm. CONCLUSIONS: Although there is a need to expand the current study to be able to calculate an exact enhancement ratio, an enhanced biological effect in vivo for early skin damage in the distal edge was demonstrated....
A correlative study on the frequencies of radiation-induced chromosome aberrations in somatic and germ cells of mammals
International Nuclear Information System (INIS)
Buul, P.P.W. van
A series of investigations on the correlation between the frequencies of radiation-induced chromosome aberrations in somatic and germ cells of mouse and rhesus monkey is described. In the mouse the induction of reciprocal translocations in bone-marrow cells was compared with that in spermatogonia (as scored in the descending spermatocytes). In the rhesus monkey frequencies of radiation-induced chromosome aberrations in spermatogonia and peripheral blood lymphocytes were studied. Furthermore the effect of multigeneration irradiation (69 generations with 200 rads X-rays) on the sensitivity for translocation induction in spermatogonia of male mice was studied. Frequencies of dicentric chromosomes and chromosomal deletions in cultured peripheral blood lymphocytes of 5 different types of mice were determined following in vitro irradiation with doses of 100 and/or 200 rad X-rays. To obtain more insight into the processes underlying translocation induction in spermatogonia of the mouse, fractionation experiments were conducted
Jégu, Teddy; Aeby, Eric; Lee, Jeannie T
Extensive 3D folding is required to package a genome into the tiny nuclear space, and this packaging must be compatible with proper gene expression. Thus, in the well-hierarchized nucleus, chromosomes occupy discrete territories and adopt specific 3D organizational structures that facilitate interactions between regulatory elements for gene expression. The mammalian X chromosome exemplifies this structure-function relationship. Recent studies have shown that, upon X-chromosome inactivation, active and inactive X chromosomes localize to different subnuclear positions and adopt distinct chromosomal architectures that reflect their activity states. Here, we review the roles of long non-coding RNAs, chromosomal organizational structures and the subnuclear localization of chromosomes as they relate to X-linked gene expression.
Next generation sequencing identifies abnormal Y chromosome and candidate causal variants in premature ovarian failure patients.
Lee, Yujung; Kim, Changshin; Park, YoungJoon; Pyun, Jung-A; Kwack, KyuBum
Premature ovarian failure (POF) is characterized by heterogeneous genetic causes such as chromosomal abnormalities and variants in causal genes. Recently, development of techniques made next generation sequencing (NGS) possible to detect genome wide variants including chromosomal abnormalities. Among 37 Korean POF patients, XY karyotype with distal part deletions of Y chromosome, Yp11.32-31 and Yp12 end part, was observed in two patients through NGS. Six deleterious variants in POF genes were also detected which might explain the pathogenesis of POF with abnormalities in the sex chromosomes. Additionally, the two POF patients had no mutation in SRY but three non-synonymous variants were detected in genes regarding sex reversal. These findings suggest candidate causes of POF and sex reversal and show the propriety of NGS to approach the heterogeneous pathogenesis of POF. Copyright © 2016 Elsevier Inc. All rights reserved.
The effects of chromosome rearrangements on the expression of heterochromatic genes in chromosome 2L of Drosophila melanogaster
International Nuclear Information System (INIS)
Wakimoto, B.T.; Hearn, M.G.
The light (lt) gene of Drosophila melanogaster is located at the base of the left arm of chromosome 2, within or very near centromeric heterochromatin (2Lh). Chromosome rearrangements that move the lt + gene from its normal proximal position and place the gene in distal euchromatin result in mosaic or variegated expression of the gene. The cytogenetic and genetic properties of 17 lt-variegated rearrangements induced by X radiation are described in this report. The authors show that five of the heterochromatic genes adjacent to lt are subject to inactivation by these rearrangements and that the euchromatic loci in proximal 2L are not detectably affected. The properties of the rearrangements suggest that proximity to heterochromatin is an important regulatory requirement for at least six 2Lh genes. They discuss how the properties of the position effects on heterochromatic genes relate to other proximity-dependent phenomena such as transvection
Common themes and cell type specific variations of higher order chromatin arrangements in the mouse
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Cremer Thomas
Full Text Available Abstract Background Similarities as well as differences in higher order chromatin arrangements of human cell types were previously reported. For an evolutionary comparison, we now studied the arrangements of chromosome territories and centromere regions in six mouse cell types (lymphocytes, embryonic stem cells, macrophages, fibroblasts, myoblasts and myotubes with fluorescence in situ hybridization and confocal laser scanning microscopy. Both species evolved pronounced differences in karyotypes after their last common ancestors lived about 87 million years ago and thus seem particularly suited to elucidate common and cell type specific themes of higher order chromatin arrangements in mammals. Results All mouse cell types showed non-random correlations of radial chromosome territory positions with gene density as well as with chromosome size. The distribution of chromosome territories and pericentromeric heterochromatin changed during differentiation, leading to distinct cell type specific distribution patterns. We exclude a strict dependence of these differences on nuclear shape. Positional differences in mouse cell nuclei were less pronounced compared to human cell nuclei in agreement with smaller differences in chromosome size and gene density. Notably, the position of chromosome territories relative to each other was very variable. Conclusion Chromosome territory arrangements according to chromosome size and gene density provide common, evolutionary conserved themes in both, human and mouse cell types. Our findings are incompatible with a previously reported model of parental genome separation.
Characteristics of the mouse genomic histamine H1 receptor gene
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Inoue, Isao; Taniuchi, Ichiro; Kitamura, Daisuke [Kyushu Univ., Fukuoka (Japan)] [and others
We report here the molecular cloning of a mouse histamine H1 receptor gene. The protein deduced from the nucleotide sequence is composed of 488 amino acid residues with characteristic properties of GTP binding protein-coupled receptors. Our results suggest that the mouse histamine H1 receptor gene is a single locus, and no related sequences were detected. Interspecific backcross analysis indicated that the mouse histamine H1 receptor gene (Hrh1) is located in the central region of mouse Chromosome 6 linked to microphthalmia (Mitfmi), ras-related fibrosarcoma oncogene 1 (Raf1), and ret proto-oncogene (Ret) in a region of homology with human chromosome 3p. 12 refs., 3 figs.
Distal displacement of the maxilla and the upper first molar.
Baumrind, S; Molthen, R; West, E E; Miller, D M
Data from a sample of 198 Class II cases treated with various appliances which deliver distally directed forces to the maxilla were examined to determine the frequency of absolute distal displacement of the upper first molar and of the maxilla. Analysis revealed that such distal displacement is possible and that it is, in fact, a frequent finding following treatment. Long-range stability of distal displacement was not assessed.
Distal radioulnar joint: functional anatomy, including pathomechanics.
Haugstvedt, J R; Langer, M F; Berger, R A
The distal radioulnar joint allows the human to rotate the forearm to place the hand in a desired position to perform different tasks, without interfering with the grasping function of the hand. The ulna is the stable part of the forearm around which the radius rotates; the stability of the distal radioulnar joint is provided by the interaction between ligaments, muscles and bones. The stabilizing structures are the triangular fibrocartilage complex, the ulnocarpal ligament complex, the extensor carpi ulnaris tendon and tendon sheath, the pronator quadratus, the interosseous membrane and ligament, the bone itself and the joint capsule. The purpose of this review article is to present and illustrate the current understanding of the functional anatomy and pathomechanics of this joint.
Structure and chromosomal localization of the human renal kallikrein gene
International Nuclear Information System (INIS)
Evans, B.A.; Yun, Z.X.; Close, J.A.
Glandular kallikreins are a family of proteases encoded by a variable number of genes in different mammalian species. In all species examined, however, one particular kallikrein is functionally conserved in its capacity to release the vasoactive peptide, Lys-bradykinin, from low molecular weight kininogen. This kallikrein is found in the kidney, pancreas, and salivary gland, showing a unique pattern of tissue-specific expression relative to other members of the family. The authors have isolated a genomic clone carrying the human renal kallikrein gene and compared the nucleotide sequence of its promoter region with those of the mouse renal kallikrein gene and another mouse kallikrein gene expressed in a distinct cell type. They find four sequence elements conserved between renal kallikrein genes from the two species. They have also shown that the human gene is localized to 19q13, a position analogous to that of the kallikrein gene family on mouse chromosome 7
A report from the Sixth International Mouse Genome Conference
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Brown, S. [Saint Mary`s Hospital Medical School, London (United Kingdom). Dept. of Biochemistry and Molecular Genetics
The Sixth Annual Mouse Genome Conference was held in October, 1992 at Buffalo, USA. The mouse is one of the primary model organisms in the Human Genome Project. Through the use of gene targeting studies the mouse has become a powerful biological model for the study of gene function and, in addition, the comparison of the many homologous mutations identified in human and mouse have widened our understanding of the biology of these two organisms. A primary goal in the mouse genome program has been to create a genetic map of STSs of high resolution (<1cM) that would form the basis for the physical mapping of the whole mouse genome. Buffalo saw substantial new progress towards the goal of a very high density genetic map and the beginnings of substantive efforts towards physical mapping in chromosome regions with a high density of genetic markers.
Distal Stressors and Depression among Homeless Men
Coohey, Carol; Easton, Scott D.
Depression is a common problem among homeless men that may interfere with functional tasks, such as securing stable housing, obtaining employment, and accessing health services. Previous research on depression among homeless men has largely focused on current psychosocial resources, substance abuse, and past victimization. Guided by Ensel and Lin's life course stress process model, the authors examined whether distal stressors, including victimization and exposure to parent problems in childh...
Identification of chromosome 7 inversion breakpoints in an autistic family narrows candidate region for autism susceptibility.
Cukier, Holly N; Skaar, David A; Rayner-Evans, Melissa Y; Konidari, Ioanna; Whitehead, Patrice L; Jaworski, James M; Cuccaro, Michael L; Pericak-Vance, Margaret A; Gilbert, John R
Chromosomal breaks and rearrangements have been observed in conjunction with autism and autistic spectrum disorders. A chromosomal inversion has been previously reported in autistic siblings, spanning the region from approximately 7q22.1 to 7q31. This family is distinguished by having multiple individuals with autism and associated disabilities. The region containing the inversion has been strongly implicated in autism by multiple linkage studies, and has been particularly associated with language defects in autism as well as in other disorders with language components. Mapping of the inversion breakpoints by FISH has localized the inversion to the region spanning approximately 99-108.75 Mb of chromosome 7. The proximal breakpoint has the potential to disrupt either the coding sequence or regulatory regions of a number of cytochrome P450 genes while the distal region falls in a relative gene desert. Copy number variant analysis of the breakpoint regions detected no duplication or deletion that could clearly be associated with disease status. Association analysis in our autism data set using single nucleotide polymorphisms located near the breakpoints showed no significant association with proximal breakpoint markers, but has identified markers near the distal breakpoint ( approximately 108-110 Mb) with significant associations to autism. The chromosomal abnormality in this family strengthens the case for an autism susceptibility gene in the chromosome 7q22-31 region and targets a candidate region for further investigation.
Fractures of the distal phalanx in the horse
International Nuclear Information System (INIS)
Yovich, J.V.
Fractures of the distal phalanx are an important cause of lameness referable to the foot. Depending on the fracture configuration and articular involvement, conservative or surgical treatment may be required. Fractures of the distal phalanx have been divided into six categories based on fracture configuration. Discussion of clinical features, management, and prognosis for horses with distal phalangeal fractures is presented for each fracture type
Nonunions of the distal tibia treated by reamed intramedullary nailing
Richmond, Jeffrey; Colleran, Kevin; Borens, Olivier; Kloen, Peter; Helfet, David L.
The purpose of this study is to determine the efficacy of reamed intramedullary nailing in the treatment of nonunions of the distal one-fourth of the tibia. Nonunions of the distal tibia are particularly difficult to treat given the short distal segment, the proximity to the ankle joint, and the
Management and treatment of distal ulcerative colitis
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Andrea Calafiore
Full Text Available Ulcerative colitis (UC is a chronic inflammatory condition that is confined to the colonic mucosa. Its main symptoms include diarrhea, rectal bleeding and abdominal pain. Approximately two-thirds of UC patients have disease confined distal to the splenic flexure, which can be treated effectively with topical therapy. This means the active drug can be delivered directly to the site of inflammation, limiting the systemic absorption and potential side effects. Topical treatment with aminosalicylates is the most effective approach in the treatment of these forms, provided that the formulation reaches the upper margin of the disease. Given this, the suppository formulation is the treatment of choice for proctitis and distal sigmoiditis. Thanks to their proximal spread, enemas, foams and gels represent the treatment of choice for proctosigmoiditis and for distal ulcerative colitis. Oral aminosalicylates are less effective than topical therapies in patients with active disease, while the combination of topical and oral treatment is more effective in patients refractory to topical or oral mono-therapy. Topically administered aminosalicylates play an important role in the maintenance of remission, but the long-term adhesion to therapy is poor. For this reason, the oral formulation is the first-line therapy in the maintenance of remission. Refractory patients can be treated with topical steroids or systemic steroids and TNF-alpha inhibitors in severe forms.
Distal Embolic Protection for Renal Arterial Interventions
International Nuclear Information System (INIS)
Dubel, Gregory J.; Murphy, Timothy P.
Distal or embolic protection has intuitive appeal for its potential to prevent embolization of materials generated during interventional procedures. Distal protection devices (DPDs) have been most widely used in the coronary and carotid vascular beds, where they have demonstrated the ability to trap embolic materials and, in some cases, to reduce complications. Given the frequency of chronic kidney disease in patients with renal artery stenosis undergoing stent placement, it is reasonable to propose that these devices may play an important role in limiting distal embolization in the renal vasculature. Careful review of the literature reveals that atheroembolization does occur during renal arterial interventions, although it often goes undetected. Early experience with DPDs in the renal arteries in patients with suitable anatomy suggests retrieval of embolic materials in approximately 71% of cases and renal functional improvement/stabilization in 98% of cases. The combination of platelet inhibition and a DPD may provide even greater benefit. Given the critical importance of renal functional preservation, it follows that everything that can be done to prevent atheroembolism should be undertaken including the use of DPDs when anatomically feasible. The data available at this time support a beneficial role for these devices
The Huntington disease locus is most likely within 325 kilobases of the chromosome 4p telomere
International Nuclear Information System (INIS)
Doggett, N.A.; Cheng, J.F.; Smith, C.L.; Cantor, C.R.
The genetic defect responsible for Huntington disease was originally localized near the tip of the short arm of chromosome 4 by genetic linkage to the locus D4S10. Several markers closer to Huntington disease have since been isolated, but these all appear to be proximal to the defect. A physical map that extends from the most distal of these loci, D4S90, to the telomere of chromosome 4 was constructed. This map identifies at least two CpG islands as markers for Huntington disease candidate genes and places the most likely location of the Huntington disease defect remarkably close (within 325 kilobases) to the telomere
Molecular fundamentals of chromosomal mutagenesis
International Nuclear Information System (INIS)
Ganassi, E.Eh.; Zaichkina, S.I.; Malakhova, L.V.
Precise quantitative correlation between the yield of chromosome structure damages and the yield of DNA damages is shown when comparing data on molecular and cytogenetic investigations carried out in cultural Mammalia cells. As the chromosome structure damage is to be connected with the damage of its carcass structure, then it is natural that DNA damage in loop regions is not to affect considerably the structure, while DNA damage lying on the loop base and connected with the chromosome carcass is to play a determining role in chromosomal mutagenesis. This DNA constitutes 1-2% from the total quantity of nuclear DNA. If one accepts that damages of these regions of DNA are ''hot'' points of chromosomal mutagenesis, then it becomes clear why 1-2% of preparation damages in a cell are realized in chromosome structural damages
Intraspecific chromosome variability
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N Dubinin
Full Text Available (Editorial preface. The publication is presented in order to remind us of one of dramatic pages of the history of genetics. It re-opens for the contemporary reader a comprehensive work marking the priority change from plant cytogenetics to animal cytogenetics led by wide population studies which were conducted on Drosophila polytene chromosomes. The year of the publication (1937 became the point of irretrievable branching between the directions of Old World and New World genetics connected with the problems of chromosome variability and its significance for the evolution of the species. The famous book of T. Dobzhansky (1937 was published by Columbia University in the US under the title "Genetics and the origin of species", and in the shadow of this American 'skybuilding' all other works grew dim. It is remarkable that both Dobzhansky and Dubinin come to similar conclusions about the role of chromosomes in speciation. This is not surprising given that they both might be considered as representatives of the Russian genetic school, by their birth and education. Interestingly, Dobzhansky had never referred to the full paper of Dubinin et al. (1937, though a previous short communication in Nature (1936 was included together with all former papers on the related subject. In full, the volume of the original publication printed in the Biological Journal in Moscow comprised 47 pages, in that number 41 pages of the Russian text accompanied by 16 Figs, a table and reference list, and, above all, 6 pages of the English summary. This final part in English is now reproduced in the authors' version with the only addition being the reference list in the originally printed form.
Maxillary molar distalization with the dual-force distalizer supported by mini-implants: a clinical study.
Oberti, Giovanni; Villegas, Carlos; Ealo, Martha; Palacio, John Camilo; Baccetti, Tiziano
The objective of this prospective study was to describe the clinical effects of a bone-supported molar distalizing appliance, the dual-force distalizer. The study group included 16 patients (mean age, 14.3 years) with Class II molar relationships. Study models and lateral cephalograms were taken before and after the distalizing movement to record significant dental and skeletal changes (Wilcoxon test). The average distalization time was 5 months, with a movement rate of 1.2 mm per month; the distalization amounts were 5.9 +/- 1.72 mm at the crown level and 4.4 +/- 1.41 mm at the furcation level. The average molar inclination was 5.6 degrees +/- 3.7 degrees ; this was less than the amount of inclination generated by bone-supported appliances that use single distalizing forces. The correlation between inclination and distalization was not significant, indicating predominantly bodily movement. The teeth anterior to the first molar moved distally also; the second premolars distalized an average of 4.26 mm, and the incisors retruded by 0.53 mm. The dual-force distalizer is a valid alternative distalizing appliance that generates controlled molar distalization with a good rate of movement and no loss of anchorage.
Robotic distal pancreatectomy versus conventional laparoscopic distal pancreatectomy: a comparative study for short-term outcomes.
Lai, Eric C H; Tang, Chung Ngai
Robotic system has been increasingly used in pancreatectomy. However, the effectiveness of this method remains uncertain. This study compared the surgical outcomes between robot-assisted laparoscopic distal pancreatectomy and conventional laparoscopic distal pancreatectomy. During a 15-year period, 35 patients underwent minimally invasive approach of distal pancreatectomy in our center. Seventeen of these patients had robot-assisted laparoscopic approach, and the remaining 18 had conventional laparoscopic approach. Their operative parameters and perioperative outcomes were analyzed retrospectively in a prospective database. The mean operating time in the robotic group (221.4 min) was significantly longer than that in the laparoscopic group (173.6 min) (P = 0.026). Both robotic and conventional laparoscopic groups presented no significant difference in spleen-preservation rate (52.9% vs. 38.9%) (P = 0.505), operative blood loss (100.3 ml vs. 268.3 ml) (P = 0.29), overall morbidity rate (47.1% vs. 38.9%) (P = 0.73), and post-operative hospital stay (11.4 days vs. 14.2 days) (P = 0.46). Both groups also showed no perioperative mortality. Similar outcomes were observed in robotic distal pancreatectomy and conventional laparoscopic approach. However, robotic approach tended to have the advantages of less blood loss and shorter hospital stay. Further studies are necessary to determine the clinical position of robotic distal pancreatectomy.
An innovative technique to distalize maxillary molar using microimplant supported rapid molar distalizer
Directory of Open Access Journals (Sweden)
Meenu Goel
Full Text Available Introduction: In recent years, enhancements in implants have made their use possible as a mode of absolute anchorage in orthodontic patients. In this paper, the authors have introduced an innovative technique to unilaterally distalize the upper left 1 st molar to obtain an ideal Class I molar relationship from a Class II existing molar relationship with an indigenous designed distalizer. Clinical Innovation: For effective unilateral diatalization of molar, a novel cantilever sliding jig assembly was utilized with coil spring supported by a buccally placed single micro implant. The results showed 3 mm of bodily distalization with 1 mm of intrusion and 2° of distal tipping of upper left 1 st molar in 1.5 months. Discussion: This appliance is relatively easy to insert, well-tolerated, and requires minimal patient cooperation compared to other present techniques of molar distalization. Moreover, it is particularly useful in cases that are Class II on one side and Class I on the other, with a minor midline discrepancy and nominal overjet. Patient acceptance level was reported to be within patients physiological and comfort limits.
Evolution of the Banana Genome (Musa acuminata) Is Impacted by Large Chromosomal Translocations.
Martin, Guillaume; Carreel, Françoise; Coriton, Olivier; Hervouet, Catherine; Cardi, Céline; Derouault, Paco; Roques, Danièle; Salmon, Frédéric; Rouard, Mathieu; Sardos, Julie; Labadie, Karine; Baurens, Franc-Christophe; D'Hont, Angélique
Most banana cultivars are triploid seedless parthenocarpic clones derived from hybridization between Musa acuminata subspecies and sometimes M. balbisiana. M. acuminata subspecies were suggested to differ by a few large chromosomal rearrangements based on chromosome pairing configurations in intersubspecies hybrids. We searched for large chromosomal rearrangements in a seedy M. acuminata ssp. malaccensis banana accession through mate-pair sequencing, BAC-FISH, targeted PCR and marker (DArTseq) segregation in its progeny. We identified a heterozygous reciprocal translocation involving two distal 3 and 10 Mb segments from chromosomes 01 and 04, respectively, and showed that it generated high segregation distortion, reduced recombination and linkage between chromosomes 01 and 04 in its progeny. The two chromosome structures were found to be mutually exclusive in gametes and the rearranged structure was preferentially transmitted to the progeny. The rearranged chromosome structure was frequently found in triploid cultivars but present only in wild malaccensis ssp. accessions, thus suggesting that this rearrangement occurred in M. acuminata ssp. malaccensis. We propose a mechanism for the spread of this rearrangement in Musa diversity and suggest that this rearrangement could have played a role in the emergence of triploid cultivars. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
Translocations of chromosome end-segments and facultative heterochromatin promote meiotic ring formation in evening primroses.
Golczyk, Hieronim; Massouh, Amid; Greiner, Stephan
Due to reciprocal chromosomal translocations, many species of Oenothera (evening primrose) form permanent multichromosomal meiotic rings. However, regular bivalent pairing is also observed. Chiasmata are restricted to chromosomal ends, which makes homologous recombination virtually undetectable. Genetic diversity is achieved by changing linkage relations of chromosomes in rings and bivalents via hybridization and reciprocal translocations. Although the structural prerequisite for this system is enigmatic, whole-arm translocations are widely assumed to be the mechanistic driving force. We demonstrate that this prerequisite is genome compartmentation into two epigenetically defined chromatin fractions. The first one facultatively condenses in cycling cells into chromocenters negative both for histone H3 dimethylated at lysine 4 and for C-banding, and forms huge condensed middle chromosome regions on prophase chromosomes. Remarkably, it decondenses in differentiating cells. The second fraction is euchromatin confined to distal chromosome segments, positive for histone H3 lysine 4 dimethylation and for histone H3 lysine 27 trimethylation. The end-segments are deprived of canonical telomeres but capped with constitutive heterochromatin. This genomic organization promotes translocation breakpoints between the two chromatin fractions, thus facilitating exchanges of end-segments. We challenge the whole-arm translocation hypothesis by demonstrating why reciprocal translocations of chromosomal end-segments should strongly promote meiotic rings and evolution toward permanent translocation heterozygosity. Reshuffled end-segments, each possessing a major crossover hot spot, can furthermore explain meiotic compatibility between genomes with different translocation histories.
Comparison of C. elegans and C. briggsae genome sequences reveals extensive conservation of chromosome organization and synteny.
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LaDeana W Hillier
Full Text Available To determine whether the distinctive features of Caenorhabditis elegans chromosomal organization are shared with the C. briggsae genome, we constructed a single nucleotide polymorphism-based genetic map to order and orient the whole genome shotgun assembly along the six C. briggsae chromosomes. Although these species are of the same genus, their most recent common ancestor existed 80-110 million years ago, and thus they are more evolutionarily distant than, for example, human and mouse. We found that, like C. elegans chromosomes, C. briggsae chromosomes exhibit high levels of recombination on the arms along with higher repeat density, a higher fraction of intronic sequence, and a lower fraction of exonic sequence compared with chromosome centers. Despite extensive intrachromosomal rearrangements, 1:1 orthologs tend to remain in the same region of the chromosome, and colinear blocks of orthologs tend to be longer in chromosome centers compared with arms. More strikingly, the two species show an almost complete conservation of synteny, with 1:1 orthologs present on a single chromosome in one species also found on a single chromosome in the other. The conservation of both chromosomal organization and synteny between these two distantly related species suggests roles for chromosome organization in the fitness of an organism that are only poorly understood presently.
Fiori, L M; Zouk, H; Himmelman, C; Turecki, G
Suicide completion rates are significantly higher in males than females in most societies. Although gender differences in suicide rates have been partially explained by environmental and behavioral factors, it is possible that genetic factors, through differential expression between genders, may also help explain gender moderation of suicide risk. This study investigated X-linked genes in suicide completers using a two-step strategy. We first took advantage of the genetic structure of the French-Canadian population and genotyped 722 unrelated French-Canadian male subjects, of whom 333 were suicide completers and 389 were non-suicide controls, using a panel of 37 microsatellite markers spanning the entire X chromosome. Nine haplotype windows and several individual markers were associated with suicide. Significant results aggregated primarily in two regions, one in the long arm and another in the short arm of chromosome X, limited by markers DXS8051 and DXS8102, and DXS1001 and DXS8106, respectively. The second stage of the study investigated differential brain expression of genes mapping to associated regions in Brodmann areas 8/9, 11, 44 and 46, in an independent sample of suicide completers and controls. Six genes within these regions, Rho GTPase-activating protein 6, adaptor-related protein complex 1 sigma 2 subunit, glycoprotein M6B, ribosomal protein S6 kinase 90 kDa polypeptide 3, spermidine/spermine N(1)-acetyltransferase 1 and THO complex 2, were found to be differentially expressed in suicide completers.
Chromosome Connections: Compelling Clues to Common Ancestry
Flammer, Larry
Students compare banding patterns on hominid chromosomes and see striking evidence of their common ancestry. To test this, human chromosome no. 2 is matched with two shorter chimpanzee chromosomes, leading to the hypothesis that human chromosome 2 resulted from the fusion of the two shorter chromosomes. Students test that hypothesis by looking for…
New Y chromosomes and early stages of sex chromosome ...
Indian Academy of Sciences (India)
Sep 6, 2010 ... chromosomes are evolutionary consequences of that func- tion. Given sufficient ... (for a review, see Charlesworth et al. 2005). ... In the present paper, I review sex deter- mination .... part had apparently been exchanged against the homologous ... age group III-Y chromosomes were successful while in well-.
Pure chromosome-specific PCR libraries from single sorted chromosomes
VanDevanter, D. R.; Choongkittaworn, N. M.; Dyer, K. A.; Aten, J. A.; Otto, P.; Behler, C.; Bryant, E. M.; Rabinovitch, P. S.
Chromosome-specific DNA libraries can be very useful in molecular and cytogenetic genome mapping studies. We have developed a rapid and simple method for the generation of chromosome-specific DNA sequences that relies on polymerase chain reaction (PCR) amplification of a single flow-sorted
[New anterolateral approach of distal femur for treatment of distal femoral fractures].
Zhang, Bin; Dai, Min; Zou, Fan; Luo, Song; Li, Binhua; Qiu, Ping; Nie, Tao
To assess the effectiveness of the new anterolateral approach of the distal femur for the treatment of distal femoral fractures. Between July 2007 and December 2009, 58 patients with distal femoral fractures were treated by new anterolateral approach of the distal femur in 28 patients (new approach group) and by conventional approach in 30 patients (conventional approach group). There was no significant difference in gender, age, cause of injury, affected side, type of fracture, disease duration, complication, or preoperative intervention (P > 0.05). The operation time, intraoperative blood loss, intraoperative fluoroscopy frequency, hospitalization days, and Hospital for Special Surgery (HSS) score of knee were recorded. Operation was successfully completed in all patients of 2 groups, and healing of incision by first intention was obtained; no vascular and nerves injuries occurred. The operation time and intraoperative fluoroscopy frequency of new approach group were significantly less than those of conventional approach group (P 0.05). All patients were followed up 12-36 months (mean, 19.8 months). Bone union was shown on X-ray films; the fracture healing time was (12.62 +/- 2.34) weeks in the new approach group and was (13.78 +/- 1.94) weeks in the conventional approach group, showing no significant difference (t=2.78, P=0.10). The knee HSS score at last follow-up was 94.4 +/- 4.2 in the new approach group, and was 89.2 +/- 6.0 in the conventional approach group, showing significant difference between 2 groups (t=3.85, P=0.00). New anterolateral approach of the distal femur for distal femoral fractures has the advantages of exposure plenitude, minimal tissue trauma, and early function rehabilitation training so as to enhance the function recovery of knee joint.
Distal protection filter device efficacy with carotid artery stenting: comparison between a distal protection filter and a distal protection balloon.
Iko, Minoru; Tsutsumi, Masanori; Aikawa, Hiroshi; Matsumoto, Yoshihisa; Go, Yoshinori; Nii, Kouhei; Abe, Gorou; Ye, Iwae; Nomoto, Yasuyuki; Kazekawa, Kiyoshi
This retrospective study aimed to compare the effectiveness of the embolization prevention mechanism of two types of embolic protection device (EPD)-a distal protection balloon (DPB) and a distal protection filter (DPF). Subjects were 164 patients scheduled to undergo carotid artery stenting: a DPB was used in 82 cases (DPB group) from April 2007 until June 2010, and a DPF was used in 82 cases (DPF group) from July 2010 to July 2011. Rates of positive findings on postoperative diffusion-weighted imaging (DWI) and stroke incidence were compared. Positive postoperative DWI results were found in 34 cases in the DPB group (41.4 %), but in only 22 cases in the DPF group (26.8 %), and there was only a small significant difference within the DPF group. In the DPB group, there was one case of transient ischemic attack (TIA) (1.2 %) and four cases of brain infarction (2 minor strokes, 2 major strokes; 4.9 %), compared to the DFP group with one case of TIA (1.2 %) and no cases of minor or major strokes. In this study, significantly lower rates of occurrence of DWI ischemic lesions and intraoperative embolization were associated with use of the DPF compared to the DPB.
Cohesin in determining chromosome architecture
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Haering, Christian H., E-mail: firstname.lastname@example.com [Cell Biology and Biophysics Unit, European Molecular Biology Laboratory (EMBL), Heidelberg (Germany); Jessberger, Rolf, E-mail: email@example.com [Institute of Physiological Chemistry, Dresden University of Technology, Dresden (Germany)
Cells use ring-like structured protein complexes for various tasks in DNA dynamics. The tripartite cohesin ring is particularly suited to determine chromosome architecture, for it is large and dynamic, may acquire different forms, and is involved in several distinct nuclear processes. This review focuses on cohesin's role in structuring chromosomes during mitotic and meiotic cell divisions and during interphase.
Sex chromosomes in Ephestia kuehniella
Czech Academy of Sciences Publication Activity Database
Marec, František; Sahara, K.; Traut, W.
Roč. 44, č. 1 (2001), s. 131 ISSN 0003-3995. [European Cytogenetics Conference /3./. 07.07.2001-10.07.2001, Paris] Institutional research plan: CEZ:AV0Z5007907 Keywords : Telomere * sex chromosomes * chromosome fragments Subject RIV: EB - Genetics ; Molecular Biology
Slit scan flow cytometry of isolated chromosomes following fluorescence hybridization: an approach of online screening for specific chromosomes and chromosome translocations
Hausmann, M.; Dudin, G.; Aten, J. A.; Heilig, R.; Diaz, E.; Cremer, C.
The recently developed methods of non radioactive in situ hybridization of chromosomes offer new aspects for chromosome analysis. Fluorescent labelling of hybridized chromosomes or chromosomal subregions allows to facilitate considerably the detection of specific chromosomal abnormalities. For many
Genetic conflict outweighs heterogametic incompatibility in the mouse hybrid zone?
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Dufková Petra
Full Text Available Abstract Background The Mus musculus musculus/M. m. domesticus contact zone in Europe is characterised by sharp frequency discontinuities for sex chromosome markers at the centre of wider clines in allozyme frequencies. Results We identify a triangular area (approximately 330 km2 where the musculus Y chromosome introgresses across this front for up to 22 km into domesticus territory. Introgression of the Y chromosome is accompanied by a perturbation of the census sex ratio: the sex ratio is significantly female biased in musculus localities and domesticus localities lacking Y chromosome introgression. In contrast, where the musculus Y is detected in domesticus localities, the sex ratio is close to parity, and significantly different from both classes of female biased localities. The geographic position of an abrupt cline in an X chromosome marker, and autosomal clines centred on the same position, seem unaffected by the musculus Y introgression. Conclusion We conclude that sex ratio distortion is playing a role in the geographic separation of speciation genes in this section of the mouse hybrid zone. We suggest that clines for genes involved in sex-ratio distortion have escaped from the centre of the mouse hybrid zone, causing a decay in the barrier to gene flow between the two house mouse taxa.
Mini-implant-supported Molar Distalization
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Amit Goyal
Full Text Available Temporary anchorage devices popularly called mini-implants or miniscrews are the latest addition to an orthodontist′s armamentarium. The following case report describes the treatment of a 16-year-old girl with a pleasant profile, moderate crowding and Angle′s Class II molar relationship. Maxillary molar distalization was planned and mini-implants were used to preserve the anterior anchorage. After 13 months of treatment, Class I molar and canine relation was achieved bilaterally and there was no anterior proclination. Thus, mini-implants provide a viable option to the clinician to carry out difficult tooth movements without any side effects.
Periosteal osteoblastoma of the distal femur
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Nakatani, Tetsuya; Yamamoto, Tetsuji; Akisue, Toshihiro; Marui, Takashi; Hitora, Toshiaki; Kawamoto, Teruya; Nagira, Keiko; Yoshiya, Shinichi; Kurosaka, Masahiro [Department of Orthopaedic Surgery, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe (Japan); Fujita, Ikuo; Matsumoto, Keiji [Department of Orthopaedic Surgery, Hyogo Medical Center for Adults, Akashi, Hyogo (Japan)
Osteoblastomas located on the surface of the cortical bone, so-called periosteal osteoblastomas, are extremely rare. We report on a case of periosteal osteoblastoma arising from the posterior surface of the right distal femur in a 17-year-old man. Roentgenographic, computed tomographic, magnetic resonance imaging, and histologic features of the case are presented. Periosteal osteoblastoma should be radiologically and histologically differentiated from myositis ossificans, avulsive cortical irregularity syndrome, osteoid osteoma, parosteal osteosarcoma, periosteal osteosarcoma, and high-grade surface osteosarcoma. Although periosteal osteoblastoma is rare, this tumor should be included in the differential diagnosis of surface-type bone tumors. (orig.)
The 5T mouse multiple myeloma model: Absence of c-myc oncogene rearrangement in early transplant generations
Radl, J.; Punt, Y.A.; Enden-Vieveen, M.H.M. van den; Bentvelzen, P.A.J.; Bakkus, M.H.C.; Akker T., W. van den; Benner, R.
Consistent chromosomal translocations involving the c-myc cellular oncogene and one of the three immunoglobulin loci are typical for human Burkitt's lymphoma, induced mouse plasmacytoma (MPC) and spontaneously arising rat immunocytoma (RIC). Another plasma cell malignancy, multiple myeloma (MM),
The murine retinoblastoma homolog maps to chromosome 14 near Es-10
Stone, J.C.; Crosby, J.J.; Kozak, C.A.; Schievella, A.R.; Bernards, R.A.; Nadeau, J.H.
Restriction fragment length variants have been exploited to map genetically Rb-1, the murine homolog of the human retinoblastoma gene. Rb-1 localized to mouse chromosome 14 on the basis of results from analysis of somatic cell hybrids. In an interspecific backcross involving Mus spretus, Rb-1 and
Krypton laser-induced photothrombotic distal middle cerebral artery occlusion without craniectomy in mice.
Sugimori, Hiroshi; Yao, Hiroshi; Ooboshi, Hiroaki; Ibayashi, Setsuro; Iida, Mitsuo
Recent advances in genetical engineering of the mouse have highlighted the importance of reproducible and less invasive models of cerebral ischemia in mice. In this paper, we developed minimally invasive and reproducible model of distal middle cerebral artery (MCA) occlusion in mice using krypton (Kr) laser-induced photothrombosis. C57BL/6 or BALB mice (n=8 each) were anesthetized with halothane. The skin was cut, the temporal muscle was retracted, and the right distal MCA was observed through the skull. A Kr laser beam of wavelength 568 nm was focused onto the MCA over the intact skull. Upon laser irradiation, intravenous administration of a rose bengal solution was begun. After 4 min of irradiation, the laser beam was refocused on the MCA just proximal to the first spot, and another 4-min irradiation was performed. Then, the right common carotid artery (CCA) was ligated. Three days later, the brain was removed, and infarct volume was determined. Infarction confined almost solely to the cortical area was produced in each mouse. Mean infarct volume in C57BL/6 mice was 25.2+/-13.7 mm3. The BALB mice group showed significantly larger and more reproducible infarction (44.1+/-5.2 mm3; the coefficient of variation was 12%) than did C57BL/6 mice (P<0.005). Our photothrombosis model of stroke in mice can be performed without craniectomy, and its reproducibility is satisfactory when using BALB mice.
Schizophrenia and chromosomal deletions
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Lindsay, E.A.; Baldini, A. [Baylor College of Medicine, Houston, TX (United States); Morris, M. A. [Univ. of Geneva School of Medicine, NY (United States)] [and others
Recent genetic linkage analysis studies have suggested the presence of a schizophrenia locus on the chromosomal region 22q11-q13. Schizophrenia has also been frequently observed in patients affected with velo-cardio-facial syndrome (VCFS), a disorder frequently associated with deletions within 22q11.1. It has been hypothesized that psychosis in VCFS may be due to deletion of the catechol-o-methyl transferase gene. Prompted by these observations, we screened for 22q11 deletions in a population of 100 schizophrenics selected from the Maryland Epidemiological Sample. Our results show that there are schizophrenic patients carrying a deletion of 22q11.1 and a mild VCFS phenotype that might remain unrecognized. These findings should encourage a search for a schizophrenia-susceptibility gene within the deleted region and alert those in clinical practice to the possible presence of a mild VCFS phenotype associated with schizophrenia. 9 refs.
CRISPR/Cas9-induced transgene insertion and telomere-associated truncation of a single human chromosome for chromosome engineering in CHO and A9 cells.
Uno, Narumi; Hiramatsu, Kei; Uno, Katsuhiro; Komoto, Shinya; Kazuki, Yasuhiro; Oshimura, Mitsuo
Chromosome engineering techniques including gene insertion, telomere-associated truncation and microcell-mediated chromosome transfer (MMCT) are powerful tools for generation of humanised model animal, containing megabase-sized genomic fragments. However, these techniques require two cell lines: homologous recombination (HR)-proficient DT40 cells for chromosome modification, and CHO cells for transfer to recipient cells. Here we show an improved technique using a combination of CRISPR/Cas9-induced HR in CHO and mouse A9 cells without DT40 cells following MMCT to recipient cells. Transgene insertion was performed in CHO cells with the insertion of enhanced green fluorescence protein (EGFP) using CRISPR/Cas9 and a circular targeting vector containing two 3 kb HR arms. Telomere-associated truncation was performed in CHO cells using CRISPR/Cas9 and a linearised truncation vector containing a single 7 kb HR arm at the 5' end, a 1 kb artificial telomere at the 3' end. At least 11% and 6% of the targeting efficiency were achieved for transgene insertion and telomere-associated truncation, respectively. The transgene insertion was also confirmed in A9 cells (29%). The modified chromosomes were transferrable to other cells. Thus, this CHO and A9 cell-mediated chromosome engineering using the CRISPR/Cas9 for direct transfer of the modified chromosome is a rapid technique that will facilitate chromosome manipulation.
Relationship between chromosome configurations/associations and nuclear size/shape
International Nuclear Information System (INIS)
Ostashevsky, J.Y.
Full text: Chromosome configurations (linear,folded,loop,etc.,which are defined through a pattern of centromere and/or telomere anchoring to the nuclear membrane) and chromosome associations (homologous pairing, number of centromere or telomere clusters per nucleus, number of chromosome arms per cluster, etc.) are critical for the formation of radiation-induced chromosome aberrations and DSB repair. However, the rules of nuclear architecture are poorly understood. A polymer approach for chromosome configurations, associations, and attachments was developed, based on the coil-like behavior of chromosomal fibers and the tight packing of discrete chromatin domains in a nucleus. The model considers chromatin anchoring to nuclear structures and shows that confinement of chromatin diffusion in a nucleus can be related to its anchoring and higher-order chromatin structure. The model was applied to nuclei of budding and fission yeast, Drosophila, worm, newt, mammals (human, Indian and Chinese muntjac, mouse) and plants (Arabidopsis, maize, barley, wheat). Quantitative agreement between results calculated from the model and observed data was obtained in all considered (∼25) cases. This supports the model and means that permitted chromosome configurations and associations can be predicted from the geometrical constraints imposed on chromosomes by nuclear size and shape
Radiographic anatomy of the distal dural SAC
International Nuclear Information System (INIS)
Larsen, J.L.; Olsen, K.O.
A radio-anatomical study was performed of the distal dural sac (DS) in 121 patients subjected to myelography. In 83.4% the termination of the DS was located from the upper half of the S1-segment to the lower half of the S2-segment. In the remaining patients the dural terminations were more distally located. The average location of the DS-termination was higher than that found in a previous anatomic study. The inference is that in patients with low-back pain and sciatica, the DS tends to terminate at a higher spinal level than in a non-selected anatomic material. The caudal reduction in sagittal diameter of the DS was less than that of the frontal diameter of the sac. The linear diminution in cross-sectional area of the DS from the level of L3 towards the lumbosacral junction was not correlated with the degree of caudal extension of the DS into the sacrum. Thus the length of the DS and its transverse diameters are independent of each other. These results supported the view that the location of the termination of the DS (and hence that of the spinal cord) is not related to stenosis of the central spinal canal. (orig.)
Maxillary molar distalization with first class appliance.
Ramesh, Namitha; Palukunnu, Biswas; Ravindran, Nidhi; Nair, Preeti P
Non-extraction treatment has gained popularity for corrections of mild-to-moderate class II malocclusion over the past few decades. The distalization of maxillary molars is of significant value for treatment of cases with minimal arch discrepancy and mild class II molar relation associated with a normal mandibular arch and acceptable profile. This paper describes our experience with a 16-year-old female patient who reported with irregularly placed upper front teeth and unpleasant smile. The patient was diagnosed to have angles class II malocclusion with moderate maxillary anterior crowding, deep bite of 4 mm on a skeletal class II base with an orthognathic maxilla and retrognathic mandible and normal growth pattern. She presented an ideal profile and so molar distalization was planned with the first-class appliance. Molars were distalised by 8 mm on the right and left quadrants and class I molar relation achieved within 4 months. The space gained was utilised effectively to align the arch and establish a class I molar and canine relation.
Dermal pocketing following distal finger replantation.
Puhaindran, Mark E; Paavilainen, Pasi; Tan, David M K; Peng, Yeong Pin; Lim, Aymeric Y T
Replantation is an ideal technique for reconstruction following fingertip amputation as it provides 'like for like' total reconstruction of the nail complex, bone pulp tissue and skin with no donor-site morbidity. However, fingertips are often not replanted because veins cannot be found or are thought to be too small to repair. Attempts at 'cap-plasty' or pocketing of replanted tips with and without microvascular anastomosis have been done in the past with varying degrees of success. We prospectively followed up a group of patients who underwent digital replantation and dermal pocketing in the palm to evaluate the outcome of this procedure. There were 10 patients with 14 amputated digits (two thumbs, five index, four middle, two ring and one little) who underwent dermal pocketing of the amputated digit following replantation. Among the 14 digits that were treated with dermal pocketing, 11 survived completely, one had partial atrophy and two were completely lost. Complications encountered included finger stiffness (two patients) and infection of the replanted fingertip with osteomyelitis of the distal phalanx (one patient). We believe that this technique can help increase the chance of survival for distal replantation with an acceptable salvage rate of 85% in our series. Copyright 2009 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.
Osteoid osteoma of the distal clavicle
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Bernardo Barcellos Terra
Full Text Available ABSTRACT The osteoid osteoma is a bone tumor that accounts for 10% of benign tumors. It was described in 1935 by Jaffe, as a tumor that affects the young adult population, with a predominance of males. This study aims to present a case of late diagnosis of a patient with osteoid osteoma of the distal clavicle region. Female patient, 44 years old, non-professional volleyball player, reported pain in the anterior and superior region of the shoulder girdle, specifically in the acromioclavicular joint, which worsened at night and had been treated for nine months as tendinitis of the rotator cuff and acromioclavicular joint arthritis. After confirming the diagnosis, the patient underwent open surgery with resection of the distal clavicle. At two years of follow-up, the patient presents without local pain. In the radiographic evaluation, coracoclavicular distance is preserved and there are no signs of recurrence. Tumors of the shoulder girdle are rare and are often diagnosed late. A high degree of suspicion for the diagnosis of tumors of the shoulder girdle is needed in order to avoid late diagnosis.
Biotin absorption by distal rat intestine
International Nuclear Information System (INIS)
Bowman, B.B.; Rosenberg, I.H.
We used the in vivo intestinal loop approach, with short (10-min) and long (3-h) incubations, to examine biotin absorption in proximal jejunum, distal ileum, cecum and proximal colon. In short-term studies, luminal biotin disappearance from rat ileum was about half that observed in the jejunum, whereas absorption by proximal colon was about 12% of that in the jejunum. In 3-h closed-loop studies, the absorption of 1.0 microM biotin varied regionally. Biotin absorption was nearly complete in the small intestine after 3 h; however, only about 15% of the dose had been absorbed in the cecum and 27% in the proximal colon after 3 h. Independent of site of administration, the major fraction of absorbed biotin was recovered in the liver; measurable amounts of radioactive biotin were also present in kidney and plasma. The results support the potential nutritional significance for the rat of biotin synthesized by bacteria in the distal intestine, by demonstrating directly an absorptive capability of mammalian large bowel for this vitamin
[Distal ureteral lithiasis. ESWL versus ambulatory URS].
Miján Ortiz, J L; Gutiérrez Tejero, F; López Carmona, F; Nogueras Ocaña, M; Arrabal Martín, M; Zuluaga Gómez, A
To present the results achieved in the treatment of 1802 distal ureteral stones treated at the Lithotripsy Unit of the San Cecilio University Hospital over the last 10 years (1990-2000). Stones were treated by extracorporeal shock wave lithotripsy (ESWL) or ureteroscopy (URS). ESWL was the initial treatment in 81% of the cases (1460 calculi) and URS in the remaining 19% (342 stones). URS was performed for complication or failed ESWL (102 stones) and ESWL was performed for failed URS, basically due to stone migration (24 stones). Ureterolithotomy was required on 7 occasions. Sedation-analgesia with fentanyl and midazolam was routinely used in URS. Sedation was required in only 55% of the ESWL procedures. Elective ESWL resolved 93% of the cases, a percentage which is similar to that achieved with URS as first treatment. The ESWL retreatment rate was 1.3. URS was successful in 98% of the cases of failed ESWL. There are two treatment modalities for stones in the distal ureter: ESWL and URS. We advocate the use of outpatient URS with sedation preferably in the female patient, impacted stones, obstructive uropathy, stones larger than 2 cm and radiotransparent stones.
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Dema Rajaiah
Full Text Available AIMS AND OBJECTIVES To study the fractures of distal end of femur and the mechanism of injury in distal end femur fractures, the advantages and disadvantages of open reduction and internal fixation of distal end femur fractures by distal femoral locking compression plate osteosynthesis and to analyse the outcome in terms of range of Knee motion, time to union, and limb shortening. RESULTS The mean age of patient is 44 years, 85% are males, road traffic accidents account for majority (80%, right side involved in 70%, Muller's type C fracture is common, good range of movements is seen 90% of cases and union occurred in 95% in 5 months. The results were assessed using Neer's score, seven (35% patients had excellent results, eight (40% patients had good results, four (20% patients had fair results and one (5% patient had poor result. CONCLUSION From our study, we conclude that DF-LCP is a safe and reliable implant and has shown excellent to satisfactory results in majority of intra-articular fractures (AO type C. Fixation with locking compression plate showed more effectiveness in severely osteoporotic bones, shorter operative stay, faster recovery, faster union rates and excellent functional outcome.
Mitotic chromosome condensation in vertebrates
International Nuclear Information System (INIS)
Vagnarelli, Paola
Work from several laboratories over the past 10–15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292–301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories—a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307–316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119–1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579–589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different
Mitotic chromosome condensation in vertebrates
Energy Technology Data Exchange (ETDEWEB)
Vagnarelli, Paola, E-mail: email@example.com
Work from several laboratories over the past 10-15 years has revealed that, within the interphase nucleus, chromosomes are organized into spatially distinct territories [T. Cremer, C. Cremer, Chromosome territories, nuclear architecture and gene regulation in mammalian cells, Nat. Rev. Genet. 2 (2001) 292-301 and T. Cremer, M. Cremer, S. Dietzel, S. Muller, I. Solovei, S. Fakan, Chromosome territories-a functional nuclear landscape, Curr. Opin. Cell Biol. 18 (2006) 307-316]. The overall compaction level and intranuclear location varies as a function of gene density for both entire chromosomes [J.A. Croft, J.M. Bridger, S. Boyle, P. Perry, P. Teague,W.A. Bickmore, Differences in the localization and morphology of chromosomes in the human nucleus, J. Cell Biol. 145 (1999) 1119-1131] and specific chromosomal regions [N.L. Mahy, P.E. Perry, S. Gilchrist, R.A. Baldock, W.A. Bickmore, Spatial organization of active and inactive genes and noncoding DNA within chromosome territories, J. Cell Biol. 157 (2002) 579-589] (Fig. 1A, A'). In prophase, when cyclin B activity reaches a high threshold, chromosome condensation occurs followed by Nuclear Envelope Breakdown (NEB) [1]. At this point vertebrate chromosomes appear as compact structures harboring an attachment point for the spindle microtubules physically recognizable as a primary constriction where the two sister chromatids are held together. The transition from an unshaped interphase chromosome to the highly structured mitotic chromosome (compare Figs. 1A and B) has fascinated researchers for several decades now; however a definite picture of how this process is achieved and regulated is not yet in our hands and it will require more investigation to comprehend the complete process. From a biochemical point of view a vertebrate mitotic chromosomes is composed of DNA, histone proteins (60%) and non-histone proteins (40%) [6]. I will discuss below what is known to date on the contribution of these two different classes
Preimplantation diagnosis of repeated miscarriage due to chromosomal translocations using metaphase chromosomes of a blastomere biopsied from 4- to 6-cell-stage embryos.
Tanaka, Atsushi; Nagayoshi, Motoi; Awata, Shoichiro; Mawatari, Yoshifumi; Tanaka, Izumi; Kusunoki, Hiroshi
To evaluate the safety and accuracy of karyotyping the blastomere chromosomes at metaphase in the natural cell cycle for preimplantation diagnosis. A pilot study. A private infertility clinic and a university laboratory. Eleven patients undergoing IVF and preimplantation diagnosis. Intact human embryos at the 4- to 6-cell stage and human-mouse heterokaryons were cultured and checked hourly for disappearance of the nuclear envelope. After it disappeared, the metaphase chromosomes were analyzed by fluorescence in situ hybridization. Percentage of analyzable metaphase plates and safety and accuracy of the method. The success rate of electrofusion to form human-mouse heterokaryons was 87.1% (27/31), and analyzable chromosomes were obtained from 77.4% (24/31) of the heterokaryons. On the other hand, disappearance of the nuclear envelope occurred in 89.5% (17/19) of the human embryos and it began earlier than that in the heterokaryons. Analyzable chromosomes were obtained and their translocation sites were identified in all blastomeres biopsied from the 17 embryos. After the biopsy, 67.0% of the embryos could develop to the blastocyst stage. The natural cell cycle method reported herein requires frequent observation, but it is safe, with no artificial effects on the chromosomes and without loss of or damage to blastomeres, which occurred with the electrofusion method. Using the natural cell cycle method, we could perform preimplantation diagnosis with nearly 100% accuracy.
Intraspecies Competition for Niches in the Distal Gut Dictate Transmission during Persistent Salmonella Infection
Lam, Lilian H.; Monack, Denise M.
In order to be transmitted, a pathogen must first successfully colonize and multiply within a host. Ecological principles can be applied to study host-pathogen interactions to predict transmission dynamics. Little is known about the population biology of Salmonella during persistent infection. To define Salmonella enterica serovar Typhimurium population structure in this context, 129SvJ mice were oral gavaged with a mixture of eight wild-type isogenic tagged Salmonella (WITS) strains. Distinct subpopulations arose within intestinal and systemic tissues after 35 days, and clonal expansion of the cecal and colonic subpopulation was responsible for increases in Salmonella fecal shedding. A co-infection system utilizing differentially marked isogenic strains was developed in which each mouse received one strain orally and the other systemically by intraperitoneal (IP) injection. Co-infections demonstrated that the intestinal subpopulation exerted intraspecies priority effects by excluding systemic S. Typhimurium from colonizing an extracellular niche within the cecum and colon. Importantly, the systemic strain was excluded from these distal gut sites and was not transmitted to naïve hosts. In addition, S. Typhimurium required hydrogenase, an enzyme that mediates acquisition of hydrogen from the gut microbiota, during the first week of infection to exert priority effects in the gut. Thus, early inhibitory priority effects are facilitated by the acquisition of nutrients, which allow S. Typhimurium to successfully compete for a nutritional niche in the distal gut. We also show that intraspecies colonization resistance is maintained by Salmonella Pathogenicity Islands SPI1 and SPI2 during persistent distal gut infection. Thus, important virulence effectors not only modulate interactions with host cells, but are crucial for Salmonella colonization of an extracellular intestinal niche and thereby also shape intraspecies dynamics. We conclude that priority effects and
Cloning an expressed gene shared by the human sex chromosomes
International Nuclear Information System (INIS)
Darling, S.M.; Banting, G.S.; Pym, B.; Wolfe, J.; Goodfellow, P.N.
The existence of genes shared by mammalian sex chromosomes has been predicted on both evolutionary and functional grounds. However, the only experimental evidence for such genes in humans is the cell-surface antigen encoded by loci on the X and Y chromosomes (MIC2X and MIC2Y, respectively), which is recognized by the monoclonal antibody 12E7. Using the bacteriophage λgt11 expression system in Escherichia coli and immunoscreening techniques, the authors have isolated a cDNA clone whose primary product is recognized by 12E7. Southern blot analysis using somatic cell hybrids containing only the human X or Y chromosomes shows that the sequences reacting with the cDNA clone are localized to the sex chromosomes. In addition, the clone hybridizes to DNAs isolated from mouse cells that have been transfected with human DNA and selected for 12E7 expression on the fluorescence-activated cell sorter. The authors conclude that the cDNA clone encodes the 12E7 antigen, which is the primary product of the MIC2 loci. The clone was used to explore sequence homology between MIC2X and MIC2Y; these loci are closely related, if not identical
Distal Communication by Chimpanzees (Pan troglodytes): Evidence for Common Ground?
Leavens, David A; Reamer, Lisa A; Mareno, Mary Catherine; Russell, Jamie L; Wilson, Daniel; Schapiro, Steven J; Hopkins, William D
van der Goot et al. (2014) proposed that distal, deictic communication indexed the appreciation of the psychological state of a common ground between a signaler and a receiver. In their study, great apes did not signal distally, which they construed as evidence for the human uniqueness of a sense of common ground. This study exposed 166 chimpanzees to food and an experimenter, at an angular displacement, to ask, "Do chimpanzees display distal communication?" Apes were categorized as (a) proximal or (b) distal signalers on each of four trials. The number of chimpanzees who communicated proximally did not statistically differ from the number who signaled distally. Therefore, contrary to the claim by van der Goot et al., apes do communicate distally. © 2015 The Authors. Child Development © 2015 Society for Research in Child Development, Inc.
Gametocidal chromosomes enhancing chromosome aberration in common wheat induced by 5-azacytidine.
Su, W-Y; Cong, W-W; Shu, Y-J; Wang, D; Xu, G-H; Guo, C-H
The gametocidal (Gc) chromosome from Aegilops spp induces chromosome mutation, which is introduced into common wheat as a tool of chromosome manipulation for genetic improvement. The Gc chromosome functions similar to a restriction-modification system in bacteria, in which DNA methylation is an important regulator. We treated root tips of wheat carrying Gc chromosomes with the hypomethylation agent 5-azacytidine; chromosome breakage and micronuclei were observed in these root tips. The frequency of aberrations differed in wheat containing different Gc chromosomes, suggesting different functions inducing chromosome breakage. Gc chromosome 3C caused the greatest degree of chromosome aberration, while Gc chromosome 3C(SAT) and 2C caused only slight chromosome aberration. Gc chromosome 3C induced different degrees of chromosome aberration in wheat varieties Triticum aestivum var. Chinese Spring and Norin 26, demonstrating an inhibition function in common wheat.
Distal renal tubular acidosis and hepatic lipidosis in a cat.
Brown, S A; Spyridakis, L K; Crowell, W A
Clinical and laboratory evidence of hepatic failure was found in a chronically anorectic cat. Simultaneous blood and urine pH determinations established a diagnosis of distal renal tubular acidosis. The cat did not respond to treatment. Necropsy revealed distal tubular nephrosis and hepatic lipidosis. The finding of distal renal tubular acidosis in a cat with hepatic lipidosis emphasizes the importance of complete evaluation of acid-base disorders in patients.
Wrist Hypothermia Related to Continuous Work with a Computer Mouse: A Digital Infrared Imaging Pilot Study
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Jelena Reste
Full Text Available Computer work is characterized by sedentary static workload with low-intensity energy metabolism. The aim of our study was to evaluate the dynamics of skin surface temperature in the hand during prolonged computer mouse work under different ergonomic setups. Digital infrared imaging of the right forearm and wrist was performed during three hours of continuous computer work (measured at the start and every 15 minutes thereafter in a laboratory with controlled ambient conditions. Four people participated in the study. Three different ergonomic computer mouse setups were tested on three different days (horizontal computer mouse without mouse pad; horizontal computer mouse with mouse pad and padded wrist support; vertical computer mouse without mouse pad. The study revealed a significantly strong negative correlation between the temperature of the dorsal surface of the wrist and time spent working with a computer mouse. Hand skin temperature decreased markedly after one hour of continuous computer mouse work. Vertical computer mouse work preserved more stable and higher temperatures of the wrist (>30 °C, while continuous use of a horizontal mouse for more than two hours caused an extremely low temperature (<28 °C in distal parts of the hand. The preliminary observational findings indicate the significant effect of the duration and ergonomics of computer mouse work on the development of hand hypothermia.
Structural variations of chromosome 1 R from rye cultivar Jingzhouheimai induced by irradiation
International Nuclear Information System (INIS)
Wang Conglei; Zhuang Lifang; Qi Zengjun
Irradiated with 60 Co γ-rays (12 Gy), the pollen of wheat landrace Huixianhong-Secale cereal cv. Jingzhouheimai DA1R was pollinated to the emasculated spikes of Huixianhong. Analyzed with genomic in situ hybridization GISH using gDNA of rye cv. Jingzhouheimai as a probe, four plants with reciprocal translocation, four plants with large segmental translocation and one plant with distal segmental translocation, one plant with one telocentric chromosome were identified from 33 M 1 seeds. The results showed that the translocation frequency was 30.30% and of the total 11 breakage-fusion events, 1 involved centric regions and 10 involved interstitial regions. The experiment showed that pollen irradiation was an effective method to induce wheat alien chromosomal structural variations which could effectively by used in deletion mapping, chromosomal location of important agronomic genes and development of small segmental translocations with target genes. (authors)
Frequent gene conversion events between the X and Y homologous chromosomal regions in primates
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Hirai Hirohisa
Full Text Available Abstract Background Mammalian sex-chromosomes originated from a pair of autosomes. A step-wise cessation of recombination is necessary for the proper maintenance of sex-determination and, consequently, generates a four strata structure on the X chromosome. Each stratum shows a specific per-site nucleotide sequence difference (p-distance between the X and Y chromosomes, depending on the time of recombination arrest. Stratum 4 covers the distal half of the human X chromosome short arm and the p-distance of the stratum is ~10%, on average. However, a 100-kb region, which includes KALX and VCX, in the middle of stratum 4 shows a significantly lower p-distance (1-5%, suggesting frequent sequence exchanges or gene conversions between the X and Y chromosomes in humans. To examine the evolutionary mechanism for this low p-distance region, sequences of a corresponding region including KALX/Y from seven species of non-human primates were analyzed. Results Phylogenetic analysis of this low p-distance region in humans and non-human primate species revealed that gene conversion like events have taken place at least ten times after the divergence of New World monkeys and Catarrhini (i.e., Old World monkeys and hominoids. A KALY-converted KALX allele in white-handed gibbons also suggests a possible recent gene conversion between the X and Y chromosomes. In these primate sequences, the proximal boundary of this low p-distance region is located in a LINE element shared between the X and Y chromosomes, suggesting the involvement of this element in frequent gene conversions. Together with a palindrome on the Y chromosome, a segmental palindrome structure on the X chromosome at the distal boundary near VCX, in humans and chimpanzees, may mediate frequent sequence exchanges between X and Y chromosomes. Conclusion Gene conversion events between the X and Y homologous regions have been suggested, mainly in humans. Here, we found frequent gene conversions in the
Analysis of morphine responses in mice reveals a QTL on Chromosome 7 [version 1; referees: 2 approved
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Wim E. Crusio
Full Text Available In this study we identified a quantitative trait locus (QTL on mouse Chromosome 7 associated with locomotor activity and rearing post morphine treatment. This QTL was revealed after correcting for the effects of another QTL peak on Chromosome 10 using composite interval mapping. The positional candidate genes are Syt9 and Ppfibp2. Several other genes within the interval are linked to neural processes, locomotor activity, and the defensive response to harmful stimuli.
Analysis of morphine responses in mice reveals a QTL on Chromosome 7 [version 2; referees: 2 approved
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Wim E. Crusio
Full Text Available In this study we identified a quantitative trait locus (QTL on mouse Chromosome 7 associated with locomotor activity and rearing post morphine treatment. This QTL was revealed after correcting for the effects of another QTL peak on Chromosome 10 using composite interval mapping. The positional candidate genes are Syt9 and Ppfibp2. Several other genes within the interval are linked to neural processes, locomotor activity, and the defensive response to harmful stimuli.
Voncken, J.W.
Human Philadelphia-positive leukemia results from a balanced chromosomal translocation, which fuses the BCR gene on chromosome 22 to the ABL proto-oncogene on chromosome 9. The understanding of Ph-positive leukemogenesis has advanced enormously over
Post-transplant distal limb syndrome
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María Florencia Borghi Torzillo
Full Text Available The post-transplant distal limb syndrome is a not well known entity, with a prevalence of 5% in patients with renal transplant. Its diagnosis is based on clinical symptoms, bone scintigraphy and MRI, it has a benign course and the patient recovers without sequel. We present the case of a 37-year-old male, with medical history of hypertension, Berger's disease in 1999 that required dialysis three times a week for four years (2009-2013 and renal transplant in 2013. The patient consults on January 2014 referring severe pain in both feet, with sudden onset; he remembers the exact date of the beginning of the pain and denies trauma, pain prevents ambulation. The bone scintigraphy shows pathological uptake in both feet with no difference between the two. Although there is no treatment for this disease, it has a benign course
Studies on the effects of radiation on enzyme activity and chromosome in mammals (Mus musuculus)
International Nuclear Information System (INIS)
Kim, J.B.; Lee, K.S.; Kim, Y.J.
From the results of many researches in radiation biology, it is well known that the radiation induces gene mutation, aberration of chromosome which is a carrier of genes and the increase or decrease of enzyme activities in living organisms. However, the frequency of chromosomal aberration or the degree of enzyme activities according to the animal's age when they are irradiated with radiation and time pass after irradiation are known a little if any. From these viewpoints, the research on the frequencies of chromosomal aberrations in bone marrow cells and the degree of activities of glucose-6-phosphate dehydrogenase in liver, kidney and brain, and isocitrate dehydrogense in kidney and brain of mouse has been carried out according to the mice age when they are irradiated with 200 rad of whole body irradiation. The chromosomes and enzyme activities were observed at 24 hours, 48 hours and 4 days to 90 days after irradiation. (Author)
Mapping of the Pim-1 oncogene in mouse t-haplotypes and its use to define the relative map positions of the tcl loci t0(t6) and tw12 and the marker tf (tufted).
Ark, B; Gummere, G; Bennett, D; Artzt, K
Pim-1 is an oncogene activated in mouse T-cell lymphomas induced by Moloney and AKR mink cell focus (MCF) viruses. Pim-1 was previously mapped to chromosome 17 by somatic cell hybrids, and subsequently to the region between the hemoglobin alpha-chain pseudogene 4 (Hba-4ps) and the alpha-crystalline gene (Crya-1) by Southern blot analysis of DNA obtained from panels of recombinant inbred strains. We have now mapped Pim-1 more accurately in t-haplotypes by analysis of recombinant t-chromosomes. The recombinants were derived from Tts6tf/t12 parents backcrossed to + tf/ + tf, and scored for recombination between the loci of T and tf. For simplicity all t-complex lethal genes properly named tcl-tx are shortened to tx. The Pim-1 gene was localized 0.6 cM proximal to the tw12 lethal gene, thus placing the Pim-1 gene 5.2 cM distal to the H-2 region in t-haplotypes. Once mapped, the Pim-1 gene was used as a marker for further genetic analysis of t-haplotypes. tw12 is so close to tf that even with a large number of recombinants it was not possible to determine whether it is proximal or distal to tf. Southern blot analysis of DNA from T-tf recombinants with a separation of tw12 and tf indicated that tw12 is proximal to tf. The mapping of two allelic t-lethals, t0 and t6 with respect to tw12 and tf has also been a problem.(ABSTRACT TRUNCATED AT 250 WORDS)
Chromosome fragility in Freemartin cattle
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V. Barbieri
Full Text Available The aim of the present study was to verify chromosome fragility in freemartin cattle using chromosome aberration (CA and sister chromatid exchange (SCE tests. A total of eighteen co-twins were investigated. Fourteen animals were identified as cytogenetically chimeric (2n=60, XX/XY while 4 were classified as normal. Freemartin cattle showed a higher percentage of aneuploid cells (18.64% and highly significant statistical differences (P < 0.001 in mean values of gaps (4.53 ± 2.05, chromatid breaks (0.26 ± 0.51, and significant statistical differences (P < 0.005 in mean values of chromosome breaks (0.12 ± 0.43 when compared to 10 control animals from single births (aneuploid cells, 11.20%; gaps, 2.01 ± 1.42; chromatid breaks, 0.05 ± 0.22; chromosome breaks, 0.02 ± 0.14.
Flow cytogenetics and chromosome sorting.
Cram, L S
This review of flow cytogenetics and chromosome sorting provides an overview of general information in the field and describes recent developments in more detail. From the early developments of chromosome analysis involving single parameter or one color analysis to the latest developments in slit scanning of single chromosomes in a flow stream, the field has progressed rapidly and most importantly has served as an important enabling technology for the human genome project. Technological innovations that advanced flow cytogenetics are described and referenced. Applications in basic cell biology, molecular biology, and clinical investigations are presented. The necessary characteristics for large number chromosome sorting are highlighted. References to recent review articles are provided as a starting point for locating individual references that provide more detail. Specific references are provided for recent developments.
Localization of introduced genes on the chromosomes of transgenic barley, wheat and triticale by fluorescence in situ hybridization
DEFF Research Database (Denmark)
Pedersen, C.; Zimny, J.; Becker, D.
Using fluorescence in situ hybridization (FISH) we localized introduced genes on metaphase chromosomes of barley, wheat, and triticale transformed by microprojectile bombardment of microspores and scutellar tissue with the pDB1 plasmid containing the uidA and bar genes. Thirteen integration sites...... of single-copy integrations. There was a slight tendency towards the localization of transgenes in distal chromosome regions. Using the GAA-satellite sequence for chromosome banding, the chromosomes containing the inserted genes were identified in most cases. Two barley lines derived from the same...... transformant showed a totally different integration pattern. Southern analysis confirmed that the inserted genes were segregating independently, resulting in different integration patterns among the progeny lines. The application of the FISH technique for the analysis of transgenic plants is discussed....
Algorithm for sorting chromosomal aberrations
DEFF Research Database (Denmark)
Vogel, Ida; Lund, Najaaraq; Rasmussen, Steen
Prenatal diagnostic methods and screening procedures change rapidly in these years. Years ago only karyotyping was performed prenatally, and we monitored only Down syndrome(1) . Since then the diagnostic possibilities have increased to QF-PCR, FISH, MLPA and chromosomal microarray.......Prenatal diagnostic methods and screening procedures change rapidly in these years. Years ago only karyotyping was performed prenatally, and we monitored only Down syndrome(1) . Since then the diagnostic possibilities have increased to QF-PCR, FISH, MLPA and chromosomal microarray....
Assignment of genes to chromosome 4 of the River buffalo with a panel of buffalo-hamster hybrid cells.
Nahas, S M; Hondt, H A; Othman, O S; Bosma, A A; Haan, N A
To identify the river buffalo chromosome carrying the genes coding for GAPD, TPI1, and LDHB, karyotypic examination was carried out on 14 buffalo-hamster hybrid clones previously tested for presence of this syntenic group. In cattle, this group (U3) has been assigned to chromosome 5, which is assumed to be homologous to the long arm of buffalo chromosome 4. Chromosome 4 was present in all five clones expressing the three enzymes, and absent in all seven negative clones, indicating that in the buffalo GAPD, TPI1, and LDHB are located on chromosome 4. One clone, expressing GAPD and TPI1, but not LDHB, was found to carry a translocation between hamster marker chromosome M(2) and buffalo 4q1 → 4qter. In another clone, expressing LDHB, but not GAPD and TPI1, chromosome 4 was absent, while a very small, unidentifiable acrocentric was present. These observations suggest that LDHB is located in the proximal part of 4q1, and that GAPD and TPI1 are located more distally, in 4q1 → 4q2. ZUSAMMENFASSUNG: Lokalisierung von Genen auf Chromosom 4 des Flußbüffels durch Büffel-Hamster-Hybridzellen Zur Identifikation von Flußbüffelchromosomen mit Genen für GAPD, TPI1 und LDHB wurden Karyotypenbestimmungen an 14 Büffel-Hamster-Hybridklonen durchgeführt, die vorher auf Anwesenheit der betreffenden synthenischen Gruppen geprüft worden waren. Bei Rindern wird diese Gruppe (U3) dem Chromosom 5 zugeordnet, welches als homolog mit dem langen Arm des Büffelchromosoms 4 betrachtet wird. Chromosom 4 war in allen fünf Klonen, die die drei Enzyme exprimiert haben, vorhanden und fehlte in allen sieben negativen klonen, so daß angenommen werden kann, daß sich bei Büffeln GAPD, TPI1 und LDHB auf Chromosom 4 befinden. Bei einem Klon, der GAPD und TPI1, aber nicht LDHB zeigte, wurde eine Translokation zwischen dem Hamstermarkerchromosom M2 und Büffel 4q1 → 4qter gefunden. Im einem anderen Klon, der LDHB, nicht aber GAPD und TPI1 zeigte, war Chromosom 4 nicht vorhanden, wohl aber
Comparison of standard laparoscopic distal pancreatectomy with minimally invasive distal pancreatectomy using the da Vinci S system.
Ito, Masahiro; Asano, Yukio; Shimizu, Tomohiro; Uyama, Ichiro; Horiguchi, Akihiko
Minimally invasive procedures for pancreatic pathologies are increasingly being used, including distal pancreatectomy. This study aimed to assess the indications for and outcomes of the da Vinci distal pancreatectomy procedure. We reviewed the medical records of patients who underwent pancreatic head resection from April 2009 to September 2013. Four patients (mean age, 52.7 years) underwent da Vinci distal pancreatectomy and 10 (mean age, 68.0 +/- 12.1 years) underwent laparoscopic distal pancreatectomy. The mean surgical duration was 292 +/- 153 min and 306 +/- 29 min, the mean blood loss was 153 +/- 71 mL and 61.7 +/- 72 mL, and the mean postoperative length of stay was 24 +/- 11 days and 14 +/- 3 days in the da Vinci distal pancreatectomy and laparoscopic distal pancreatectomy groups, respectively. One patient who underwent da Vinci distal pancreatectomy developed a pancreatic fistula, while 2 patients in the laparoscopic distal pancreatectomy group developed splenic ischemia and gastric torsion, respectively. Laparoscopic and robotic pancreatic resection were both safe and feasible in selected patients with distal pancreatic pathologies. Further studies are necessary to clarify the role of robotic surgery in the advanced laparoscopic era.
Diagnostic radiation and chromosome aberrations
International Nuclear Information System (INIS)
Patil, S.R.; Hecht, F.; Lubs, H.A.; Kimberling, W.; Brown, J.; Gerald, P.S.; Summitt, R.L.
Some evidence is presented suggesting that diagnostic X-rays may be important in the origin of a new chromosomal abnormality other than Down syndrome. Chromosome analyses have been carried out on 4342 children, seven or eight years old. Maternal diagnostic irradiation in the year before conception and up to third lunar month of the index pregnancy was recorded, before the chromosome study began, together with a large amount of family and clinical data. Information on X-ray exposure was supplied by the mothers, s o radiation dosage could not be estimated. 21 children (including a pair of twins and a pair of siblings) born to 19 mothers had chromosomal aberrations. The mothers of six children with inherited translocations, rearrangements and XYY karyotypes were excluded, and 3 (23%) of the remaining 13 mothers had received abdominal and pelvic X-ray exposures. In the whole sample, however, only 6% of the mothers had diagnostic irradiation. Two of these mothers, aged sixteen and twenty, gave birth to a child each with de-novo autosomal translocations, and the third mother, aged thirty-two, had a child with a complex mosaicism involving one X chromosome. Although the sample size of the mothers with chromosomally abnormal children is small, the results are significant. (U.K.)
Diagnostic radiation and chromosome aberrations
Energy Technology Data Exchange (ETDEWEB)
Patil, S R; Hecht, F [Dept. of Pediatrics, Child Development and Rehabilitation Center, Univ. of Oregon Health Sciences Center, Portland, Oregon (USA); Lubs, H A; Kimberling, W; Brown, J; Gerald, P S; Summitt, R L
Some evidence is presented suggesting that diagnostic X-rays may be important in the origin of a new chromosomal abnormality other than Down syndrome. Chromosome analyses have been carried out on 4342 children, seven or eight years old. Maternal diagnostic irradiation in the year before conception and up to third lunar month of the index pregnancy was recorded, before the chromosome study began, together with a large amount of family and clinical data. Information on X-ray exposure was supplied by the mothers, so radiation dosage could not be estimated. 21 children (including a pair of twins and a pair of siblings) born to 19 mothers had chromosomal aberrations. The mothers of six children with inherited translocations, rearrangements and XYY karyotypes were excluded, and 3 (23%) of the remaining 13 mothers had received abdominal and pelvic X-ray exposures. In the whole sample, however, only 6% of the mothers had diagnostic irradiation. Two of these mothers, aged sixteen and twenty, gave birth to a child each with de-novo autosomal translocations, and the third mother, aged thirty-two, had a child with a complex mosaicism involving one X chromosome. Although the sample size of the mothers with chromosomally abnormal children is small, the results are significant.
[Comparison of laparoscopic distal pancreatectomy and open distal pancreatectomy in pancreatic ductal adenocarcinoma].
Xu, K; Su, J J; Su, M; Yan, L; Feng, J; Xin, X L; Chen, Y L
Objective: To compare and evaluate the curative effect of laparoscopic distal pancreatectomy(LDP) and traditional open distal pancreatectomy(ODP) in pancreatic ductal adenocarcinoma. Methods: The clinical data of 15 patients treated by LDP and 87 contemporaneous cases treated by ODP from January 2010 to November 2015 was collected, and the curative effect and prognosis of these patients were retrospectively analyzed. Results: The operation time of LDP group was (286.5±48.1) min, significantly longer than that of OPD group(226.6±56.8) min ( P 0.05). In both LDP group and ODP group, none occurred percutaneous drainage, re-admissions, second operation or perioperative death. Conclusions: Compared to ODP, LDP is much safer and more steady in perioperative periodand operation. Patients of pancreatic ductal adenocarcinoma received LDP can acquire more benefit and recovery sooner, and LDP is a safe and effective operative method.
Designing of plant artificial chromosome (PAC) by using the Chlorella smallest chromosome as a model system.
Noutoshi, Y; Arai, R; Fujie, M; Yamada, T
As a model for plant-type chromosomes, we have been characterizing molecular organization of the Chlorella vulgaris C-169 chromosome I. To identify chromosome structural elements including the centromeric region and replication origins, we constructed a chromosome I specific cosmid library and aligned each cosmid clones to generate contigs. So far, more than 80% of the entire chromosome I has been covered. A complete clonal physical reconstitution of chromosome I provides information on the structure and genomic organization of plant genome. We propose our strategy to construct an artificial chromosome by assembling the functional chromosome structural elements identified on Chrorella chromosome I.
Numerically abnormal chromosome constitutions in humans
Energy Technology Data Exchange (ETDEWEB)
Chapter 24, discusses numerically abnormal chromosome constitutions in humans. This involves abnormalities of human chromosome number, including polyploidy (when the number of sets of chromosomes increases) and aneuploidy (when the number of individual normal chromosomes changes). Chapter sections discuss the following chromosomal abnormalities: human triploids, imprinting and uniparental disomy, human tetraploids, hydatidiform moles, anomalies caused by chromosomal imbalance, 13 trisomy (D{sub 1} trisomy, Patau syndrome), 21 trisomy (Down syndrome), 18 trisomy syndrome (Edwards syndrome), other autosomal aneuploidy syndromes, and spontaneous abortions. The chapter concludes with remarks on the nonrandom participation of chromosomes in trisomy. 69 refs., 3 figs., 4 tabs.
An integrated genetic, physical, and transcriptional map of chromosome 13
Energy Technology Data Exchange (ETDEWEB)
Scheffer, H.; Kooy, R.F.; Wijngaard, A. [Univ. of Groningen (Netherlands)] [and others
In this study a genetic map containing 20 markers and typed in 40 CEPH families is presented. It includes 7 thusfar untyped microsatellite markers, 7 that have previously been mapped on a subset of 8 CEPH families, one reference marker, D13S71, and three telomeric VNTR markers. Also, 4 intragenic RB1 markers were typed. The markers have an average heterozygosity of 73% (80%, excluding the three RFLPs). The total sex average length of the map is 140 cM. The mean female to male ratio is 1.54. For the non-telomeric part of the chromosome between the markers D13S221 in 13q12 and D13S173 in 13q33-q34, this ratio is 1.99. This ratio is reversed in the telomeric part of the chromosome between D13S173 and D13S234 in distal 13q34, where it is 0.47. A high new mutation frequency of 1% was detected in the (CTTT(T)){sub n} repeat in intron 20 of the RB1 gene. The map has been integrated with 7 microsatellite markers and 2 RFLP markers from CEPH database version 7.0, resulting in a map with 32 markers (28 loci) of chromosome 13q. In addition, a deletion hybrid breakpoint map ordering 50 markers in 18 intervals is constructed. It includes 32 microsatellite markers, 4 genes, 5 STSs, and 9 ESTs. Each of 18 intervals contains at least one microsatellite marker included in the extended genetic map. These data allow a correlation between the genetic and physical map of chromosome 13. New ESTs are currently being identified and localized at this integrated map.
Increased high-density lipoprotein cholesterol levels in mice with XX versus XY sex chromosomes.
Link, Jenny C; Chen, Xuqi; Prien, Christopher; Borja, Mark S; Hammerson, Bradley; Oda, Michael N; Arnold, Arthur P; Reue, Karen
The molecular mechanisms underlying sex differences in dyslipidemia are poorly understood. We aimed to distinguish genetic and hormonal regulators of sex differences in plasma lipid levels. We assessed the role of gonadal hormones and sex chromosome complement on lipid levels using the four core genotypes mouse model (XX females, XX males, XY females, and XY males). In gonadally intact mice fed a chow diet, lipid levels were influenced by both male-female gonadal sex and XX-XY chromosome complement. Gonadectomy of adult mice revealed that the male-female differences are dependent on acute effects of gonadal hormones. In both intact and gonadectomized animals, XX mice had higher HDL cholesterol (HDL-C) levels than XY mice, regardless of male-female sex. Feeding a cholesterol-enriched diet produced distinct patterns of sex differences in lipid levels compared with a chow diet, revealing the interaction of gonadal and chromosomal sex with diet. Notably, under all dietary and gonadal conditions, HDL-C levels were higher in mice with 2 X chromosomes compared with mice with an X and Y chromosome. By generating mice with XX, XY, and XXY chromosome complements, we determined that the presence of 2 X chromosomes, and not the absence of the Y chromosome, influences HDL-C concentration. We demonstrate that having 2 X chromosomes versus an X and Y chromosome complement drives sex differences in HDL-C. It is conceivable that increased expression of genes escaping X-inactivation in XX mice regulates downstream processes to establish sexual dimorphism in plasma lipid levels. © 2015 American Heart Association, Inc.
The Robertsonian phenomenon in the house mouse: mutation, meiosis and speciation.
Garagna, Silvia; Page, Jesus; Fernandez-Donoso, Raul; Zuccotti, Maurizio; Searle, Jeremy B
Many different chromosomal races with reduced chromosome number due to the presence of Robertsonian fusion metacentrics have been described in western Europe and northern Africa, within the distribution area of the western house mouse Mus musculus domesticus. This subspecies of house mouse has become the ideal model for studies to elucidate the processes of chromosome mutation and fixation that lead to the formation of chromosomal races and for studies on the impact of chromosome heterozygosities on reproductive isolation and speciation. In this review, we briefly describe the history of the discovery of the first and subsequent metacentric races in house mice; then, we focus on the molecular composition of the centromeric regions involved in chromosome fusion to examine the molecular characteristics that may explain the great variability of the karyotype that house mice show. The influence that metacentrics exert on the nuclear architecture of the male meiocytes and the consequences on meiotic progression are described to illustrate the impact that chromosomal heterozygosities exert on fertility of house mice-of relevance to reproductive isolation and speciation. The evolutionary significance of the Robertsonian phenomenon in the house mouse is discussed in the final section of this review.
Mechanisms of induction of chromosomal aberrations and their detection by fluorescence in situ hybridization
International Nuclear Information System (INIS)
Natarajan, A.T.
Recently introduced fluorescence in situ hybridization (FISH) technique employing chromosome specific DNA libraries as well as region specific DNA probes (e.g., centromere, telomere) have helped to analyse chromosomal aberrations in great detail and thus have given some new insights into the mechanisms of induction of chromosomal aberrations. The relative proportion of induction of translocations and dicentrics by ionising radiation was studied in human, mice and Chinese hamster cells. Many of the studies point to the differences between the mechanisms of induction of dicentrics and translocations. Preliminary results obtained in our laboratory using arm specific probes for human chromosomes 1 and 3 indicate that the aberrations between the arms appear to be more than expected on a random basis. By employing telomeric probes the frequencies of interstitial deletions were found to be high and similar to the frequencies of dicentrics both in human and mouse lymphocytes. A recent study with human chromosome specific probes clearly shows variation of sensitivity of chromosomes for the induction of exchange aberrations. Radiation response studies with Chinese hamster cells using telomeric probes, suggest that telomeric sequences, especially interstitial ones appear to be an important factor in the origin of both spontaneous and induced chromosomal aberrations
Chromosome 11-linked determinant controls fetal globin expression and the fetal-to-adult globin switch
International Nuclear Information System (INIS)
Melis, M.; Demopulos, G.; Najfeld, V.; Zhang, J.W.; Brice, M.; Papayannopoulou, T.; Stamatoyannopoulos, G.
Hybrids formed by fusing mouse erythroleukemia (MEL) cells with human fetal erythroid cells produce human fetal globin, but they switch to adult globin production as culture time advances. To obtain information on the chromosomal assignment of the elements that control γ-to-β switching, the authors analyzed the chromosomal composition of hybrids producing exclusively or predominantly human fetal globin and hybrids producing only adult human globin. No human chromosome was consistently present in hybrids expressing fetal globin and consistently absent in hybrids expressing adult globin. Subcloning experiments demonstrated identical chromosomal compositions in subclones displaying the fetal globin program and those that had switched to expression of the adult globin program. These data indicate that retention of only one human chromosome -- i.e., chromosome 11 -- is sufficient for expression of human fetal globin and the subsequent γ-to-β switch. The results suggest that the γ-to-β switch is controlled either cis to the β-globin locus of by a trans-acting mechanism, the genes of which reside on human chromosome 11
Mirror-symmetric duplicated chromosome 21q with minor proximal deletion, and with neocentromere in a child without the classical Down syndrome phenotype.
Barbi, G; Kennerknecht, I; Wöhr, G; Avramopoulos, D; Karadima, G; Petersen, M B
We report on a mentally retarded child with multiple minor anomalies and an unusually rearranged chromosome 21. This der(21) chromosome has a deletion of 21p and of proximal 21q, whereas the main portion of 21q is duplicated leading to a mirror-symmetric appearance with the mirror axis at the breakpoint. The centromere is only characterized by a secondary constriction (with a centromeric index of a G chromosome) at an unexpected distal position, but fluorescence in situ hybridization (FISH) with either chromosome specific or with all human centromeres alpha satellite DNA shows no cross hybridization. Thus, the marker chromosome represents a further example of an "analphoid marker with neocentromere." Molecular analysis using polymorphic markers on chromosome 21 verified a very small monosomic segment of the proximal long arm of chromosome 21, and additionally trisomy of the remaining distal segment. Although trisomic for almost the entire 21q arm, our patient shows no classical Down syndrome phenotype, but only a few minor anomalies found in trisomy 21 and in monosomy of proximal 21q, respectively. Copyright 2000 Wiley-Liss, Inc.
Transfer of Hessian fly resistance from rye to wheat via radiation-induced terminal and intercalary chromosomal translocations
International Nuclear Information System (INIS)
Friebe, B.; Hatchett, J.H.; Gill, B.S.; Mukai, Y.; Sebesta, E.E.
A new Hessian fly (Mayetiola destructor) resistance gene derived from 'Balbo' rye and its transfer to hexaploid wheat via radiation-induced terminal and intercalary chromosomal translocations are described. Crosses between resistant 'Balbo' rye and susceptible 'Suwon 92' wheat and between the F1 amphidiploids and susceptible 'TAM 106' and 'Amigo' wheats produced resistant BC2F3 lines that were identified by C-banding analysis as being 6RL telocentric addition lines. Comparative chromosomal analyses and resistance tests revealed that the resistance gene is located on the 6RL telocentric chromosome. X-irradiated pollen of 6RL addition plants was used to fertilize plants of susceptible wheats 'TAM 106,' 'TAM 101,' and 'Vona.' After several generations of selection for resistance, new sublines were obtained that were homogeneous for resistance. Thirteen of these lines were analyzed by C-banding, and three different wheat-6RL chromosomal translocations (T) were identified. Wheat chromosomes involved in the translocations were 6B, 4B, and 4A. Almost the complete 6RL arm is present in T6BS · 6BL-6RL. Only the distal half of 6RL is present in T4BS · 4BL-6RL, which locates the resistance gene in the distal half of 6RL. Only a very small segment (ca 1.0 μm) of the distal region of 6RL is present in an intercalary translocation (Ti) Ti4AS · 4AL-6RL-4AL. The 6RL segment is inserted in the intercalary region between the centromere of chromosome 4A and the large proximal C-band of 4AL. The break-points of the translocations are outside the region of the centromere, indicating that they were induced by the X-ray treatment. All three translocations are cytologically stable and can be used directly in wheat breeding programs
The role of sex chromosomes in mammalian germ cell differentiation: can the germ cells carrying X and Y chromosomes differentiate into fertile oocytes?
Directory of Open Access Journals (Sweden)
Teruko Taketo
Full Text Available The sexual differentiation of germ cells into spermatozoa or oocytes is strictly regulated by their gonadal environment, testis or ovary, which is determined by the presence or absence of the Y chromosome, respectively. Hence, in normal mammalian development, male germ cells differentiate in the presence of X and Y chromosomes, and female germ cells do so in the presence of two X chromosomes. However, gonadal sex reversal occurs in humans as well as in other mammalian species, and the resultant XX males and XY females can lead healthy lives, except for a complete or partial loss of fertility. Germ cells carrying an abnormal set of sex chromosomes are efficiently eliminated by multilayered surveillance mechanisms in the testis, and also, though more variably, in the ovary. Studying the molecular basis for sex-specific responses to a set of sex chromosomes during gametogenesis will promote our understanding of meiotic processes contributing to the evolution of sex determining mechanisms. This review discusses the fate of germ cells carrying various sex chromosomal compositions in mouse models, the limitation of which may be overcome by recent successes in the differentiation of functional germ cells from embryonic stem cells under experimental conditions.
Mouse Y-Encoded Transcription Factor Zfy2 Is Essential for Sperm Head Remodelling and Sperm Tail Development
Vernet, Nadege; Mahadevaiah, Shantha K.; Decarpentrie, Fanny; Longepied, Guy; de Rooij, Dirk G.; Burgoyne, Paul S.; Mitchell, Michael J.
A previous study indicated that genetic information encoded on the mouse Y chromosome short arm (Yp) is required for efficient completion of the second meiotic division (that generates haploid round spermatids), restructuring of the sperm head, and development of the sperm tail. Using mouse models
Young Children's Sibling Relationship Quality: Distal and Proximal Correlates
Kretschmer, Tina; Pike, Alison
Background: Relationships within families are interdependent and related to distal environmental factors. Low socioeconomic status (SES) and high household chaos (distal factors) have been linked to less positive marital and parent-child relationships, but have not yet been examined with regard to young children's sibling relationships. The…
Distal clavicular osteolysis: MR evidence for subchondral fracture
Energy Technology Data Exchange (ETDEWEB)
Kassarjian, Ara; Palmer, William E. [Massachusetts General Hospital, Department of Radiology, Division of Musculoskeletal Radiology, Yawkey Center, Boston, MA (United States); Llopis, Eva [Hospital de la Ribera, Department of Radiology, Valencia (Spain)
To investigate the association between distal clavicular osteolysis and subchondral fractures of the distal clavicle at MRI. This study was approved by the hospital human research committee, which waived the need for informed consent. Three radiologists retrospectively analyzed 36 shoulder MR examinations in 36 patients with imaging findings of distal clavicular osteolysis. The presence of a subchondral fracture of the distal clavicle, abnormalities of the acromioclavicular joint, rotator cuff tears and labral tears were assessed by MRI. These cases were then compared with 36 age-matched controls. At MRI, 31 of 36 patients (86%) had a subchondral line within the distal clavicular edema, consistent with a subchondral fracture. Of the 36 patients, 32 (89%) had fluid in the acromioclavicular joint, while 27 of 36 patients (75%) had cysts or erosions in the distal clavicle. There were 13 patients (36%) with associated labral tears, while eight patients (22%) had partial-thickness rotator cuff tears. In the control group one of 36 (3%) had a subchondral line (P<0.05), while ten of 36 (28%) had rotator cuff tears and 13 of 36 (36%) had labral tears. These latter two were not statistically significant between the groups. A distal clavicular subchondral fracture is a common finding in patients with imaging evidence of distal clavicular osteolysis. These subchondral fractures may be responsible for the propensity of findings occurring on the clavicular side of the acromioclavicular joint. (orig.)
Distal clavicular osteolysis: MR evidence for subchondral fracture
International Nuclear Information System (INIS)
Kassarjian, Ara; Palmer, William E.; Llopis, Eva
To investigate the association between distal clavicular osteolysis and subchondral fractures of the distal clavicle at MRI. This study was approved by the hospital human research committee, which waived the need for informed consent. Three radiologists retrospectively analyzed 36 shoulder MR examinations in 36 patients with imaging findings of distal clavicular osteolysis. The presence of a subchondral fracture of the distal clavicle, abnormalities of the acromioclavicular joint, rotator cuff tears and labral tears were assessed by MRI. These cases were then compared with 36 age-matched controls. At MRI, 31 of 36 patients (86%) had a subchondral line within the distal clavicular edema, consistent with a subchondral fracture. Of the 36 patients, 32 (89%) had fluid in the acromioclavicular joint, while 27 of 36 patients (75%) had cysts or erosions in the distal clavicle. There were 13 patients (36%) with associated labral tears, while eight patients (22%) had partial-thickness rotator cuff tears. In the control group one of 36 (3%) had a subchondral line (P<0.05), while ten of 36 (28%) had rotator cuff tears and 13 of 36 (36%) had labral tears. These latter two were not statistically significant between the groups. A distal clavicular subchondral fracture is a common finding in patients with imaging evidence of distal clavicular osteolysis. These subchondral fractures may be responsible for the propensity of findings occurring on the clavicular side of the acromioclavicular joint. (orig.)
Intra-articular osteotomy for distal humerus malunion
Marti, René K.; Doornberg, Job
Intra-articular osteotomy is considered in the rare case of malunion after a fracture of the distal humerus to restore humeral alignment and gain a functional arc of elbow motion. Traumatic and iatrogenic disruption of the limited blood flow to the distal end of the humerus resulting in avascular
Clinical relevance of distal biceps insertional and footprint anatomy
van den Bekerom, Michel P J; Kodde, Izaäk F.; Aster, Asir; Bleys, Ronald L A W; Eygendaal, Denise
Purpose: The aim of this review was to present an overview, based on a literature search, of surgical anatomy for distal biceps tendon repairs, based on the current literature. Methods: A narrative review was performed using Pubmed/Medline using key words: Search terms were distal biceps,
Distal tibiofibular synostosis in a Nigerian: A case report | Owoeye ...
African Journals Online (AJOL)
X-ray of the bones showed an oblique fracture in the distal end of the shaft of fibula which is suggestive of post traumatic tibiofibular synostosis (TFS). Knowledge of distal TFS is important in resolving the puzzle of chronic shin pain of unknown origin and in accurate diagnosis of causes of ankle deformity and malformations.
Radiographic study of distal radial physeal closure in thoroughbred horses
International Nuclear Information System (INIS)
Vulcano, L.C.; Mamprim, M.J.; Muniz, L.M.R.; Moreira, A.F.; Luna, S.P.L.
Monthly radiography was performed to study distal radial physeal closure in ten male and ten female Throughbred horses. The height, thoracic circumference and metacarpus circumference were also measured, Distal radial physeal closure time was sooner in females than males, and took 701 +/- 37 and 748 +/- 55 days respectively
Sexual dimorphism in white campion: complex control of carpel number is revealed by Y chromosome deletions
International Nuclear Information System (INIS)
Lardon, A.; Georgiev, S.; Aghmir, A.; Le Merrer, G.; Negrutiu, I.
Sexual dimorphism in the dioecious plant white campion (Silene latifolia = Melandrium album) is under the control of two main regions on the Y chromosome. One such region, encoding the gynoecium-suppressing function (GSF), is responsible for the arrest of carpel initiation in male flowers. To generate chromosomal deletions, we used pollen irradiation in male plants to produce hermaphroditic mutants (bsx mutants) in which carpel development was restored. The mutants resulted from alterations in at least two GSF chromosomal regions, one autosomal and one located on the distal half of the (p)-arm of the Y chromosome. The two mutations affected carpel development independently, each mutation showing incomplete penetrance and variegation, albeit at significantly different levels. During successive meiotic generations, a progressive increase in penetrance and a reduction in variegation levels were observed and quantified at the level of the Y-linked GSF (GSF-Y). Possible mechanisms are proposed to explain the behavior of the bsx mutations: epigenetic regulation or/and second-site mutation of modifier genes. In addition, studies on the inheritance of the hermaphroditic trait showed that, unlike wild-type Y chromosomes, deleted Y chromosomes can be transmitted through both the male and the female lines. Altogether, these findings bring experimental support, on the one hand, to the existence on the Y chromosome of genic meiotic drive function(s) and, on the other hand, to models that consider that dioecy evolved through multiple mutation events. As such, the GSF is actually a system containing more than one locus and whose primary component is located on the Y chromosome
Directory of Open Access Journals (Sweden)
Manikumar C. J
Full Text Available BACKGROUND Fractures of the distal femur present considerable challenges in management. Older patients especially women sustain fractures due to osteoporosis. Supracondylar fractures of femur have a bimodal distribution. They account for 6% of all femur fractures and 31% if hip fractures were excluded. Nearly, 50% of distal femur intra-articular fractures are open fractures. Before 1970, most supracondylar fractures were treated nonoperatively; however, difficulties were often encountered including persistent angulatory deformity, knee joint incongruity, loss of knee motion and delayed mobilisation. The trend of open reduction and internal fixation has become evident in recent years with good results being obtained with AO blade plate, dynamic condylar screw, intramedullary supracondylar nail and locking compression plate. Elderly patients and osteoporosis pose difficulty in treating intra-articular fractures of the lower end of femur. Loss of stable fixation is of great concern in these cases. Hence, locking compression plate use has an advantage in these patients. MATERIALS AND METHODS In this study, 20 patients with closed fracture of distal femur were studied. All the cases were treated at the Department of Orthopaedics, Rangaraya Medical College/Government General Hospital, Kakinada, Andhra Pradesh, between November 2013 and November 2015. The method used for fracture fixation was open reduction and internal fixation with distal femoral locking plate. The duration of follow up ranged from 3 months to 24 months. All the fractures in this series were posttraumatic. The patients were functionally evaluated with Neer's scoring system. 1 RESULTS Twenty distal femoral fractures were treated with distal femoral locking plates. 15 patients were males and 5 patients were females. The median age was 47 years ranging from 28-70 years. 16 of the fractures were caused by road traffic accidents and 2 were due to fall, 2 were due to assault. 12 patients
The effect of track structure on the induction of chromosomal aberrations in murine cells
Durante, M.; Cella, L.; Furusawa, Y.; George, K.; Gialanella, G.; Grossi, G.; Pugliese, M.; Saito, M.; Yang, T. C.
PURPOSE: To measure chromosome aberrations in C3H 10T1/2 mouse fibroblasts using FISH painting at the first mitosis following exposure to 30 keV/microm hydrogen or neon ions. MATERIALS AND METHODS: Cells in plateau-phase were irradiated with 0.86 MeV protons at the TTT-3 Tandem accelerator in Naples (Italy), or with 400 MeV/n Ne ions at the HIMAC accelerator in Chiba (Japan). Colcemid-blocked cells were harvested at the first mitosis following exposure, and chromosome spreads were hybridized in situ with a fluorescein-labelled composite mouse DNA probe specific for chromosomes 2 and 8. RESULTS: Protons were more efficient than neon ions at the same LET in the induction of chromosome interchanges and breaks. Yields of complex exchanges were similar for both particles at the same dose, but protons produced mostly insertions, while with Ne exposure non-reciprocal exchanges were the most frequent complex-type exchange. CONCLUSIONS: Charged particles with the same LET produce different yields of chromosome aberrations, and some observed differences can be explained based on the available track-structure models.
Fluorescence- and NOR-studies at chromosomes of several vertebrate-species
International Nuclear Information System (INIS)
Maurer, F.
In the investigated species of fishes clear-cut Chromomycin-positive blocks were visualised. This holds true as well for Lecaspius delineatus, Gobio gobio, Perca fluciatilis, Cyprinus carpio, Carassius and auratus gibelio. In contrast, DA-DAPI-Fluorescence was homogenous along the entire chromosome. The silver-impregnation-technique proved useful in all investigated species of fisches. In the chicken certain chromosome-districts the Chromomycin-fluorescence was more pronounced than in others; Distamycin-DAPI led to a homogeneous staining along hole the arms. The investigations in mouse-chromosomes revealed an R-banding-pattern. The Distamycin-DAPI-pattern of mouse-chromosomes were complementary to the Chromomycin-pattern and strongly pronounced centromeres. Again Distmycin-DAPI-staining did not allow an unquastinable bandling resolution; simularities to Actimomycin-DAPI-fluorochrome-included patterns were observed. By means of silver-impragnation-techniques the presence of double-point-formed NOR's on more chromosomes were highlighted. However an exact destination of the number was not possible and remains reserved to further investigations. (Author)
Transmission of chromosomal and instability via a chromosome irradiated with ionizing radiation
International Nuclear Information System (INIS)
Kodama, Seiji; Tanabe, Masateru; Shiraishi, Kazunori; Oshimura, Mitsuo
We examined the stability of the transferred chromosome in 5 and 12 microcell hybrids including unirradiated human chromosomes 6 and 8, respectively, and 6 and 19 microcell hybrids including 4 Gy-irradiated human chromosomes 6 and 8, respectively. The transferred chromosome was structurally stable in most microcell hybrids transferred with the unirradiated chromosomes 6 and 8. In contrast, the 4 Gy-irradiated human chromosomes were unstable in 3 out of 6 hybrids (50%) with chromosome 6 and 3 out of 19 hybrids (16%) with chromosome 8, showing multiple aberrations in high frequencies (35∼98%). To know the cause of delayed chromosomal instability, intrachromosomal rearrangements of the human chromosome is investigated by subtelomere FISH in 17 microcell hybrids transferred with chromosomes 6 and 8. We found frequent intrachromosomal in 7 microcell hybrids (41%). However, no clear correlation was observed between the intrachromosomal rearrangements and the induction of delayed chromosomal instability by ionizing radiation
The murine ufo receptor: molecular cloning, chromosomal localization and in situ expression analysis.
Faust, M; Ebensperger, C; Schulz, A S; Schleithoff, L; Hameister, H; Bartram, C R; Janssen, J W
We have cloned the mouse homologue of the ufo oncogene. It encodes a novel tyrosine kinase receptor characterized by a unique extracellular domain containing two immunoglobulin-like and two fibronectin type III repeats. Comparison of the predicted ufo amino acid sequences of mouse and man revealed an overall identity of 87.6%. The ufo locus maps to mouse chromosome 7A3-B1 and thereby extends the known conserved linkage group between mouse chromosome 7 and human chromosome 19. RNA in situ hybridization analysis established the onset of specific ufo expression in the late embryogenesis at day 12.5 post coitum (p.c.) and localized ufo transcription to distinct substructures of a broad spectrum of developing tissues (e.g. subepidermal cells of the skin, mesenchymal cells of the periosteum). In adult animals ufo is expressed in cells forming organ capsules as well as in connective tissue structures. ufo may function as a signal transducer between specific cell types of mesodermal origin.
Retrospective dosimetry using chromosome painting
International Nuclear Information System (INIS)
Nasazzi, N.B.; Giorgio, M.D.; Taja, M.R.
Chromosome aberration frequency measured in peripheral lymphocytes of persons exposed to ionizing radiation has been used since 1960s for dose assessment. Suspected overexposure is usually evaluated by the frequency of dicentrics and centric rings using an appropriate in vitro calibration curve. However, these chromosome aberrations are unstable with time after exposure and dose reconstruction may encounter uncertainties when the time between the exposure and the analysis is considerable or even unknown. It appears that translocations persist with time after exposure and may be used as an indication of acute past overexposures. Moreover, they appear to accumulate the cytogenetical information, which correlates with the dose received under fractionated, chronic or even occupational exposure conditions. Translocations may be detected using G-banding, which allows to score the total amount of radiation induced translocations but it is a time consuming method, or by Chromosome Painting, a method base on the Fluorescence in situ Hybridization (FISH) technique, painting only some chromosome pairs with specific whole chromosome probes and then extrapolating the observed translocation frequencies to the full genome. The latter method allows a faster aberration scoring than G-banding and appears to be the most promissory tool for biodosimetry, particularly when it is necessary to assess low doses and consequently to score a large number of metaphases, e.g. radiation workers exposed within dose limits. As with the unstable chromosome aberration, it is necessary an in vitro calibration curve based on the frequency of stable chromosome aberrations to assess doses. Our laboratory performed calibration curves for Co 60 γ-rays based on the frequencies of unstable (dicentrics and centric rings detected by conventional Giemsa staining) and stable chromosome aberrations (translocations and inversions, detected by G-banding). In order to minimize the interlaboratory variability, we
Rehabilitation for distal radial fractures in adults.
Handoll, Helen H G; Elliott, Joanne
Fracture of the distal radius is a common clinical problem, particularly in older people with osteoporosis. There is considerable variation in the management, including rehabilitation, of these fractures. This is an update of a Cochrane review first published in 2002 and last updated in 2006. To examine the effects of rehabilitation interventions in adults with conservatively or surgically treated distal radial fractures. We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL 2014; Issue 12), MEDLINE, EMBASE, CINAHL, AMED, PEDro, OTseeker and other databases, trial registers, conference proceedings and reference lists of articles. We did not apply any language restrictions. The date of the last search was 12 January 2015. Randomised controlled trials (RCTs) or quasi-RCTs evaluating rehabilitation as part of the management of fractures of the distal radius sustained by adults. Rehabilitation interventions such as active and passive mobilisation exercises, and training for activities of daily living, could be used on their own or in combination, and be applied in various ways by various clinicians. The review authors independently screened and selected trials, and reviewed eligible trials. We contacted study authors for additional information. We did not pool data. We included 26 trials, involving 1269 mainly female and older patients. With few exceptions, these studies did not include people with serious fracture or treatment-related complications, or older people with comorbidities and poor overall function that would have precluded trial participation or required more intensive treatment. Only four of the 23 comparisons covered by these 26 trials were evaluated by more than one trial. Participants of 15 trials were initially treated conservatively, involving plaster cast immobilisation. Initial treatment was surgery (external fixation or internal fixation) for all participants
Distal Stressors and Depression among Homeless Men.
Coohey, Carol; Easton, Scott D
Depression is a common problem among homeless men that may interfere with functional tasks, such as securing stable housing, obtaining employment, and accessing health services. Previous research on depression among homeless men has largely focused on current psychosocial resources, substance abuse, and past victimization. Guided by Ensel and Lin's life course stress process model, the authors examined whether distal stressors, including victimization and exposure to parent problems in childhood, contributed to men's depression above and beyond current (or proximal) stressors, such as substance abuse and health problems, and social resources. The sample consisted of 309 homeless men who had entered a federally funded emergency shelter. Using the Burns Depression Checklist, the authors found that one out of three men met the threshold for moderate to severe depression during the past week. The logistic regression showed that past exposure to parent problems was related to depression after accounting for current stressors and social resources (number of close adult relationships and whether their emotional support needs were met). Past victimization was not related to depression. To address men's depression, workers should concurrently provide services that meet men's basic needs (for example, housing) and address their relationship needs, including their need for emotional support.
Radiation-induced chromosomal instability
International Nuclear Information System (INIS)
Ritter, S.
Recent studies on radiation-induced chromosomal instability in the progeny of exposed mammalian cells were briefly described as well as other related studies. For the analysis of chromosomal damage in clones, cells were seeded directly after exposure in cell well-dish to form single cell clones and post-irradiation chromosome aberrations were scored. Both exposure to isoeffective doses of X-ray or 270 MeV/u C-ions (13 keV/μm) increased the number of clones with abnormal karyotype and the increase was similar for X-ray and for C-ions. Meanwhile, in the progeny of cells for mass cultures, there was no indication of a delayed expression of chromosomal damage up to 40 population doublings after the exposure. A high number of aberrant cells were only observed directly after exposure to 10.7 MeV/u O-ions, i.e. in the first cycle cells and decreased with subsequent cell divisions. The reason for these differences in the radiation-induced chromosomal instability between clonal isolates and mass culture has not been clarified. Recent studies indicated that genomic instability occurs at a high frequency in the progeny of cells irradiated with both sparsely and densely ionizing radiation. Such genomic instability is thought likely to increase the risk of carcinogenesis, but more data are required for a well understanding of the health risks resulting from radiation-induced delayed instability. (M.N.)
Chromosome segregation in plant meiosis
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Linda eZamariola
Full Text Available Faithful chromosome segregation in meiosis is essential for ploidy stability over sexual life cycles. In plants, defective chromosome segregation caused by gene mutations or other factors leads to the formation of unbalanced or unreduced gametes creating aneuploid or polyploid progeny, respectively. Accurate segregation requires the coordinated execution of conserved processes occurring throughout the two meiotic cell divisions. Synapsis and recombination ensure the establishment of chiasmata that hold homologous chromosomes together allowing their correct segregation in the first meiotic division, which is also tightly regulated by cell-cycle dependent release of cohesin and monopolar attachment of sister kinetochores to microtubules. In meiosis II, bi-orientation of sister kinetochores and proper spindle orientation correctly segregate chromosomes in four haploid cells. Checkpoint mechanisms acting at kinetochores control the accuracy of kinetochore-microtubule attachment, thus ensuring the completion of segregation. Here we review the current knowledge on the processes taking place during chromosome segregation in plant meiosis, focusing on the characterization of the molecular factors involved.
Radiation exposure and chromosome damage
International Nuclear Information System (INIS)
Lloyd, D.
Chromosome damage is discussed as a means of biologically measuring radiation exposure to the body. Human lymphocytes are commonly used for this test since the extent of chromosome damage induced is related to the exposure dose. Several hundred lymphocytes are analysed in metaphase for chromosome damage, particularly dicentrics. The dose estimate is made by comparing the observed dicentric yield against calibration curves, previously produced by in vitro irradiation of blood samples to known doses of different types of radiation. This test is useful when there is doubt that the film badge has recorded a reasonable whole body dose and also when there is an absence of any physical data. A case of deliberate exposure is described where the chromosome damage test estimated an exposure of 152 rads. The life span of cell aberrations is also considered. Regular checks on radiotherapy patients and some accidental overdose cases have shown little reduction in the aberration levels over the first six weeks after which the damage disappears slowly with a half-life of about three years. In conclusion, chromosome studies have been shown to be of value in resolving practical problems in radiological protection. (U.K.)
Chromosomal rearrangement interferes with meiotic X chromosome inactivation
Czech Academy of Sciences Publication Activity Database
Homolka, David; Ivánek, Robert; Čapková, Jana; Jansa, Petr; Forejt, Jiří
Roč. 17, č. 10 (2007), s. 1431-1437 ISSN 1088-9051 R&D Projects: GA MŠk(CZ) 1M0520; GA ČR GA301/06/1334; GA ČR GA301/07/1383 Grant - others:Howard Hughes Medical Institute(US) HHMI 55000306 Institutional research plan: CEZ:AV0Z50520514 Keywords : chromosomal translocations * meiotic X chromosome inactivation * spermatogenesis Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 11.224, year: 2007
Does computer use affect the incidence of distal arm pain? A one-year prospective study using objective measures of computer use
DEFF Research Database (Denmark)
Mikkelsen, Sigurd; Lassen, Christina Funch; Vilstrup, Imogen
PURPOSE: To study how objectively recorded mouse and keyboard activity affects distal arm pain among computer workers. METHODS: Computer activities were recorded among 2,146 computer workers. For 52 weeks mouse and keyboard time, sustained activity, speed and micropauses were recorded with a soft......PURPOSE: To study how objectively recorded mouse and keyboard activity affects distal arm pain among computer workers. METHODS: Computer activities were recorded among 2,146 computer workers. For 52 weeks mouse and keyboard time, sustained activity, speed and micropauses were recorded...... with a software program installed on the participants' computers. Participants reported weekly pain scores via the software program for elbow, forearm and wrist/hand as well as in a questionnaire at baseline and 1-year follow up. Associations between pain development and computer work were examined for three pain...... were not risk factors for acute pain, nor did they modify the effects of mouse or keyboard time. Computer usage parameters were not associated with prolonged or chronic pain. A major limitation of the study was low keyboard times. CONCLUSION: Computer work was not related to the development...
Does computer use affect the incidence of distal arm pain? A one-year prospective study using objective measures of computer use
DEFF Research Database (Denmark)
Mikkelsen, S.; Lassen, C. F.; Vilstrup, Imogen
PURPOSE: To study how objectively recorded mouse and keyboard activity affects distal arm pain among computer workers. METHODS: Computer activities were recorded among 2,146 computer workers. For 52 weeks mouse and keyboard time, sustained activity, speed and micropauses were recorded with a soft......PURPOSE: To study how objectively recorded mouse and keyboard activity affects distal arm pain among computer workers. METHODS: Computer activities were recorded among 2,146 computer workers. For 52 weeks mouse and keyboard time, sustained activity, speed and micropauses were recorded...... with a software program installed on the participants' computers. Participants reported weekly pain scores via the software program for elbow, forearm and wrist/hand as well as in a questionnaire at baseline and 1-year follow up. Associations between pain development and computer work were examined for three pain...... were not risk factors for acute pain, nor did they modify the effects of mouse or keyboard time. Computer usage parameters were not associated with prolonged or chronic pain. A major limitation of the study was low keyboard times. CONCLUSION: Computer work was not related to the development...
Translocations of Chromosome End-Segments and Facultative Heterochromatin Promote Meiotic Ring Formation in Evening Primroses[W][OPEN
Golczyk, Hieronim; Massouh, Amid; Greiner, Stephan
Due to reciprocal chromosomal translocations, many species of Oenothera (evening primrose) form permanent multichromosomal meiotic rings. However, regular bivalent pairing is also observed. Chiasmata are restricted to chromosomal ends, which makes homologous recombination virtually undetectable. Genetic diversity is achieved by changing linkage relations of chromosomes in rings and bivalents via hybridization and reciprocal translocations. Although the structural prerequisite for this system is enigmatic, whole-arm translocations are widely assumed to be the mechanistic driving force. We demonstrate that this prerequisite is genome compartmentation into two epigenetically defined chromatin fractions. The first one facultatively condenses in cycling cells into chromocenters negative both for histone H3 dimethylated at lysine 4 and for C-banding, and forms huge condensed middle chromosome regions on prophase chromosomes. Remarkably, it decondenses in differentiating cells. The second fraction is euchromatin confined to distal chromosome segments, positive for histone H3 lysine 4 dimethylation and for histone H3 lysine 27 trimethylation. The end-segments are deprived of canonical telomeres but capped with constitutive heterochromatin. This genomic organization promotes translocation breakpoints between the two chromatin fractions, thus facilitating exchanges of end-segments. We challenge the whole-arm translocation hypothesis by demonstrating why reciprocal translocations of chromosomal end-segments should strongly promote meiotic rings and evolution toward permanent translocation heterozygosity. Reshuffled end-segments, each possessing a major crossover hot spot, can furthermore explain meiotic compatibility between genomes with different translocation histories. PMID:24681616
Centralized mouse repositories.
Donahue, Leah Rae; Hrabe de Angelis, Martin; Hagn, Michael; Franklin, Craig; Lloyd, K C Kent; Magnuson, Terry; McKerlie, Colin; Nakagata, Naomi; Obata, Yuichi; Read, Stuart; Wurst, Wolfgang; Hörlein, Andreas; Davisson, Muriel T
Because the mouse is used so widely for biomedical research and the number of mouse models being generated is increasing rapidly, centralized repositories are essential if the valuable mouse strains and models that have been developed are to be securely preserved and fully exploited. Ensuring the ongoing availability of these mouse strains preserves the investment made in creating and characterizing them and creates a global resource of enormous value. The establishment of centralized mouse repositories around the world for distributing and archiving these resources has provided critical access to and preservation of these strains. This article describes the common and specialized activities provided by major mouse repositories around the world.
Delineation and analysis of chromosomal regions specifying Yersinia pestis.
Derbise, Anne; Chenal-Francisque, Viviane; Huon, Christèle; Fayolle, Corinne; Demeure, Christian E; Chane-Woon-Ming, Béatrice; Médigue, Claudine; Hinnebusch, B Joseph; Carniel, Elisabeth
Yersinia pestis, the causative agent of plague, has recently diverged from the less virulent enteropathogen Yersinia pseudotuberculosis. Its emergence has been characterized by massive genetic loss and inactivation and limited gene acquisition. The acquired genes include two plasmids, a filamentous phage, and a few chromosomal loci. The aim of this study was to characterize the chromosomal regions acquired by Y. pestis. Following in silico comparative analysis and PCR screening of 98 strains of Y. pseudotuberculosis and Y. pestis, we found that eight chromosomal loci (six regions [R1pe to R6pe] and two coding sequences [CDS1pe and CDS2pe]) specified Y. pestis. Signatures of integration by site specific or homologous recombination were identified for most of them. These acquisitions and the loss of ancestral DNA sequences were concentrated in a chromosomal region opposite to the origin of replication. The specific regions were acquired very early during Y. pestis evolution and were retained during its microevolution, suggesting that they might bring some selective advantages. Only one region (R3pe), predicted to carry a lambdoid prophage, is most likely no longer functional because of mutations. With the exception of R1pe and R2pe, which have the potential to encode a restriction/modification and a sugar transport system, respectively, no functions could be predicted for the other Y. pestis-specific loci. To determine the role of the eight chromosomal loci in the physiology and pathogenicity of the plague bacillus, each of them was individually deleted from the bacterial chromosome. None of the deletants exhibited defects during growth in vitro. Using the Xenopsylla cheopis flea model, all deletants retained the capacity to produce a stable and persistent infection and to block fleas. Similarly, none of the deletants caused any acute flea toxicity. In the mouse model of infection, all deletants were fully virulent upon subcutaneous or aerosol infections. Therefore
A comparison between robotic-assisted laparoscopic distal pancreatectomy versus laparoscopic distal pancreatectomy.
Goh, Brian K P; Chan, Chung Yip; Soh, Hui-Ling; Lee, Ser Yee; Cheow, Peng-Chung; Chow, Pierce K H; Ooi, London L P J; Chung, Alexander Y F
This study aims to compare the early perioperative outcomes of robotic-assisted laparoscopic distal pancreatectomy (RDP) versus laparoscopic distal pancreatectomy (LDP). The clinicopathologic features of 45 consecutive patients who underwent minimally-invasive distal pancreatectomy from 2006 to 2015 were retrospectively reviewed. Thirty-nine patients who met our study criteria were included. Eight patients underwent RDP and 31 had LDP. There were 10 (25.6%) open conversions. Six (15.4%) patients had major (> grade 2) morbidities and there was no in-hospital mortality. There were 14 (35.9%) grade A and 9 (23.1%) grade B pancreatic fistulas. Comparison between RDP and LDP demonstrated no significant difference between the patients' baseline characteristics except there was increased frequency of spleen-preserving pancreatectomies (3 (37.5%) vs 25 (80.6%), P=0.016) and splenic-vessel preservation (5 (62.5%) vs 4 (12.9%), P=0.003) in RDP. Comparison between outcomes demonstrated that RDP was associated with a longer median operation time (452.5 (range, 300-685) vs 245 min (range, 85-430), P=0.001) and increased frequency of the procedure completed purely laparoscopically (8 (100%) vs 18 (58.1%), P=0.025). RDP can be safely adopted and is equivalent to LDP in most perioperative outcomes. It is also associated with a decreased frequency of the need for hand-assistance laparoscopic surgery or open conversion but needed a longer operation time. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
[A case of mosaic ring chromosome 4 with subtelomeric 4p deletion].
Kim, Jeong Hyun; Oh, Phil Soo; Na, Hye Yeon; Kim, Sun-Hee; Cho, Hyoun Chan
Ring chromosome is a structural abnormality that is thought to be the result of fusion and breakage in the short and long arms of chromosome. Wolf-Hirschhorn syndrome (WHS) is a well-known congenital anomaly in the ring chromosome 4 with a partial deletion of the distal short arm. Here we report a 10-month-old male of mosaic ring chromosome 4 with the chief complaint of severe short stature. He showed the height of -4 standard deviation, subtle hypothyroidism and mild atrial septal defect/ventricular septal defect, and also a mild language developmental delay was suspected. Brain magnetic resonance imaging showed multifocal leukomalacia. Chromosomal analysis of the peripheral blood showed the mosaic karyotype with [46,XY,r(4)(p16q35)[84]/45,XY,-4[9]/91,XXYY, dic r(4;4)(p16q35;p16q35)[5]/46,XY,dic r(4;4)(p16q35;p16q35)[2
Cytogenetic and molecular markers for detecting Aegilops uniaristata chromosomes in a wheat background.
Gong, Wenping; Li, Guangrong; Zhou, Jianping; Li, Genying; Liu, Cheng; Huang, Chengyan; Zhao, Zhendong; Yang, Zujun
Aegilops uniaristata has many agronomically useful traits that can be used for wheat breeding. So far, a Triticum turgidum - Ae. uniaristata amphiploid and one set of Chinese Spring (CS) - Ae. uniaristata addition lines have been produced. To guide Ae. uniaristata chromatin transformation from these lines into cultivated wheat through chromosome engineering, reliable cytogenetic and molecular markers specific for Ae. uniaristata chromosomes need to be developed. Standard C-banding shows that C-bands mainly exist in the centromeric regions of Ae. uniaristata but rarely at the distal ends. Fluorescence in situ hybridization (FISH) using (GAA)8 as a probe showed that the hybridization signal of chromosomes 1N-7N are different, thus (GAA)8 can be used to identify all Ae. uniaristata chromosomes in wheat background simultaneously. Moreover, a total of 42 molecular markers specific for Ae. uniaristata chromosomes were developed by screening expressed sequence tag - sequence tagged site (EST-STS), expressed sequence tag - simple sequence repeat (EST-SSR), and PCR-based landmark unique gene (PLUG) primers. The markers were subsequently localized using the CS - Ae. uniaristata addition lines and different wheat cultivars as controls. The cytogenetic and molecular markers developed herein will be helpful for screening and identifying wheat - Ae. uniaristata progeny.
Unilateral maxillary molar distalization with zygoma-gear appliance.
Kilkis, Dogan; Bayram, Mehmet; Celikoglu, Mevlut; Nur, Metin
The aim of this study was to present the orthodontic treatment of a 15-year-old boy with a unilateral maxillary molar distalization system, called the zygoma-gear appliance. It consisted of a zygomatic anchorage miniplate, an inner bow, and a Sentalloy closed coil spring (GAC International, Bohemia, NY). A distalizing force of 350 g was used during the distalization period. The unilateral Class II malocclusion was corrected in 5 months with the zygoma-gear appliance. The maxillary left first molar showed distalization of 4 mm with an inclination of 3°. The maxillary premolars moved distally with the help of the transseptal fibers. In addition, there were slight decreases in overjet (-0.5 mm) and maxillary incisor inclination (-1°), indicating no anchorage loss from the zygoma-gear appliance. Preadjusted fixed appliances (0.022 × 0.028-in, MBT system; 3M Unitek, Monrovia, Calif) were placed in both arches to achieve leveling and alignment. After 14 months of unilateral distalization with the zygoma-gear appliance and fixed appliances, Class I molar and canine relationships were established with satisfactory interdigitation of the posterior teeth. Acceptable overjet and overbite were also achieved. This article shows that this new system, the zygoma-gear appliance, can be used for unilateral maxillary molar distalization without anchorage loss. Copyright © 2012 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.
Genetic localization of Cd63, a member of the transmembrane 4 superfamily, reveals two distinct loci in the mouse genome
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Gwynn, B.; Eicher, E.M.; Peters, L.L. [Jackson Lab., Bar Harbor, ME (United States)
The membrane protein CD63, a molecular marker for early stages of melanoma progression, has been associated with platelet storage pool deficiency disorders (SPD). CD63 localizes to the membranes of platelets, lysosomes, and melanosomes, all of which are affected in a specific subgroup of SPD. The cDNA encoding CD63 detects two closely related sequences that map to different regions of the mouse genome. One locus maps to mouse Chromosome (Chr) 10 in a region that shares linkage homology with the human chromosome encoding human CD63. The second locus maps to mouse Chr 18 in a region that bears no known human CD63-related genes. No SPD has been localized to these regions of either the mouse or the human chromosomes. 15 refs., 2 figs.
Chromosomal rearrangements in Tourette syndrome
DEFF Research Database (Denmark)
Bertelsen, Birgitte; Debes, Nanette Mol; Hjermind, Lena E
, and identification of susceptibility genes through linkage and association studies has been complicated due to inherent difficulties such as no clear mode of inheritance, genetic heterogeneity, and apparently incomplete penetrance. Positional cloning through mapping of disease-related chromosome rearrangements has...... been an efficient tool for the cloning of disease genes in several Mendelian disorders and in a number of complex disorders. Through cytogenetic investigation of 205 TS patients, we identified three possibly disease-associated chromosome rearrangements rendering this approach relevant in chasing TS...
Chromosomal instability determines taxane response
DEFF Research Database (Denmark)
Swanton, C.; Nicke, B.; Schuett, M.
chromosomal instability (CIN). Silencing 22/50 of these genes, many of which are involved in DNA repair, caused cancer cell death, suggesting that these genes are involved in the survival of aneuploid cells. Overexpression of these "CIN-survival'' genes is associated with poor outcome in estrogen receptor......-positive breast cancer and occurs frequently in basal-like and Her2-positive cases. In diploid cells, but not in chromosomally unstable cells, paclitaxel causes repression of CIN-survival genes, followed by cell death. In the OV01 ovarian cancer clinical trial, a high level of CIN was associated with taxane...
Potassium transport across guinea pig distal colon
International Nuclear Information System (INIS)
Rechkemmer, G.; Halm, D.R.; Frizzell, R.A.
Active absorption and secretion of K was studied by measuring bidirectional 42 K fluxes across short-circuited guinea pig distal colon. Tissues were pretreated with mucosal (m) and serosal (s) indomethacin (1 μM) and amiloride (0.1 mM, m) to suppress spontaneous, electrogenic Cl secretion and Na absorption. Under these conditions, the short-circuit current (I/sub sc/) was 0.4 μeq/cm 2 h while electroneutral K absorption was 2.8 μeq/cm 2 h. Epinephrine (5 μM, s) stimulated electrogenic K secretion, reducing net K absorption to 1.3 μeq/cm 2 h. Bumetanide (0.1 mM, s) abolished this K secretion and restored K absorption to control values, suggesting mechanistic similarities between K and Cl secretion. K absorption was inhibited 40% by the gastric H/K ATPase inhibitor, omeprazole (0.1 mM, m), and was abolished by ouabain (0.1 mM, m). Neutral K absorption does not appear to be mediated by an apical membrane Na/K pump since: the effect of mucosal ouabain on K absorption does not require the presence of mucosal or serosal Na, unidirectional Na fluxes are not influenced by mucosal ouabain, and K absorption is not affected when Na absorption is abolished by amiloride. Net K transport is determined by the balance between electroneutral K absorption and electrogenic K secretion. The ouabain sensitivity of K absorption suggests that colonic H/K ATPase differs from its gastric counterpart
Histology of the distal dural ring.
Graffeo, Christopher S; Perry, Avital; Copeland, William R; Raghunathan, Aditya; Link, Michael J
The distal dural ring (DDR) is a conserved intracranial anatomic structure marking the boundary point at which the internal carotid artery (ICA) exits the cavernous sinus (CS) and enters the subarachnoid space. Although the CS has been well described in a range of anatomic studies, to our knowledge no prior study has analyzed the histologic relationship between the ICA and DDR. Correspondingly, our objective was to assess the relationship of the DDR to the ICA and determine whether the DDR can be dissected from the ICA and thus divided, or can only be circumferentially trimmed around the artery. The authors examined ten fresh-frozen, adult cadaveric specimens. A standard frontotemporal craniotomy, orbito-optic osteotomy, and extradural anterior clinoidectomy was performed bilaterally. The cavernous ICA, DDR, and supraclinoid ICA were harvested as an en bloc specimen. Specimens formalin-fixed and paraffin-embedded prior to routine histochemical staining with hematoxylin and eosin and Masson trichrome. In all specimens, marked microscopic investment of the DDR throughout the ICA adventitia was noted. Dural collagen fibers extensively permeated the arterial layers superficial to the muscularis propria, with no evidence of a clear separation between the DDR and arterial adventitia. Histologic analysis suggests that the ICA and DDR are highly interrelated, continuous structures, and therefore attempted intraoperative dissection between these structures may carry an elevated risk of injury to the ICA. We correspondingly recommend careful circumferential trimming of the DDR in lieu of direct dissection in cases requiring mobilization of the clinoidal ICA. Clin. Anat. 30:742-746, 2017. © 2017Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.
Two-wave propagation in in vitro swine distal ulna
Mano, Isao; Horii, Kaoru; Matsukawa, Mami; Otani, Takahiko
Ultrasonic transmitted waves were obtained in an in vitro swine distal ulna specimen, which mimics a human distal radius, that consists of interconnected cortical bone and cancellous bone. The transmitted waveforms appeared similar to the fast waves, slow waves, and overlapping fast and slow waves measured in the specimen after removing the surface cortical bone (only cancellous bone). In addition, the circumferential waves in the cortical bone and water did not affect the fast and slow waves. This suggests that the fast-and-slow-wave phenomenon can be observed in an in vivo human distal radius.
Intra-Articular Osteotomy for Distal Humerus Malunion
Directory of Open Access Journals (Sweden)
René K. Marti
Full Text Available Intra-articular osteotomy is considered in the rare case of malunion after a fracture of the distal humerus to restore humeral alignment and gain a functional arc of elbow motion. Traumatic and iatrogenic disruption of the limited blood flow to the distal end of the humerus resulting in avascular necrosis of capitellum or trochlea is a major pitfall of the this technically challenging procedure. Two cases are presented which illustrate the potential problems of intra-articular osteotomy for malunion of the distal humerus.
Structure, tissue distribution, and chromosomal localization of the prepronociceptin gene.
Mollereau, C; Simons, M J; Soularue, P; Liners, F; Vassart, G; Meunier, J C; Parmentier, M
Nociceptin (orphanin FQ), the newly discovered natural agonist of opioid receptor-like (ORL1) receptor, is a neuropeptide that is endowed with pronociceptive activity in vivo. Nociceptin is derived from a larger precursor, prepronociceptin (PPNOC), whose human, mouse, and rat genes we have now isolated. The PPNOC gene is highly conserved in the three species and displays organizational features that are strikingly similar to those of the genes of preproenkephalin, preprodynorphin, and preproopiomelanocortin, the precursors to endogenous opioid peptides, suggesting the four genes belong to the same family-i.e., have a common evolutionary origin. The PPNOC gene encodes a single copy of nociceptin as well as of other peptides whose sequence is strictly conserved across murine and human species; hence it is likely to be neurophysiologically significant. Northern blot analysis shows that the PPNOC gene is predominantly transcribed in the central nervous system (brain and spinal cord) and, albeit weakly, in the ovary, the sole peripheral organ expressing the gene. By using a radiation hybrid cell line panel, the PPNOC gene was mapped to the short arm of human chromosome 8 (8p21), between sequence-tagged site markers WI-5833 and WI-1172, in close proximity of the locus encoding the neurofilament light chain NEFL. Analysis of yeast artificial chromosome clones belonging to the WC8.4 contig covering the 8p21 region did not allow to detect the presence of the gene on these yeast artificial chromosomes, suggesting a gap in the coverage within this contig.
Partial duplication of the APBA2 gene in chromosome 15q13 corresponds to duplicon structures
Directory of Open Access Journals (Sweden)
Kesterson Robert A
Full Text Available Abstract Background Chromosomal abnormalities affecting human chromosome 15q11-q13 underlie multiple genomic disorders caused by deletion, duplication and triplication of intervals in this region. These events are mediated by highly homologous segments of DNA, or duplicons, that facilitate mispairing and unequal cross-over in meiosis. The gene encoding an amyloid precursor protein-binding protein (APBA2 was previously mapped to the distal portion of the interval commonly deleted in Prader-Willi and Angelman syndromes and duplicated in cases of autism. Results We show that this gene actually maps to a more telomeric location and is partially duplicated within the broader region. Two highly homologous copies of an interval containing a large 5' exon and downstream sequence are located ~5 Mb distal to the intact locus. The duplicated copies, containing the first coding exon of APBA2, can be distinguished by single nucleotide sequence differences and are transcriptionally inactive. Adjacent to APBA2 maps a gene termed KIAA0574. The protein encoded by this gene is weakly homologous to a protein termed X123 that in turn maps adjacent to APBA1 on 9q21.12; APBA1 is highly homologous to APBA2 in the C-terminal region and is distinguished from APBA2 by the N-terminal region encoded by this duplicated exon. Conclusion The duplication of APBA2 sequences in this region adds to a complex picture of different low copy repeats present across this region and elsewhere on the chromosome.
Loss of heterozygosity on the X chromosome in human breast cancer.
Loupart, M L; Adams, S; Armour, J A; Walker, R; Brammar, W; Varley, J
The analysis of loss of heterozygosity (LOH) in tumours can be a powerful tool for mapping the sites of tumour suppressor genes in the human genome. A panel of breast cancer patients was assembled as pairs of tumour and lymphocyte DNA samples and LOH studies carried out by Southern hybridisation with polymorphic loci mapping to the X chromosome with appropriate controls. Deletion mapping revealed a high frequency of small regionalised deletions, defining at least three independent regions, one of which is particularly well mapped to a 500 kb stretch of DNA in the distal portion of the pseudoautosomal region of Xp. A second region has been identified within the pseudoautosomal region close to the pseudoautosomal boundary, and there is a third discrete site of loss on distal Xq. Perturbations of sequences at these regions represent independent events in a number of patients. This study represents the first detailed analysis of LOH on the X chromosome in human breast tumours, the results of which indicate that at least three regions of this chromosome are involved in the disease.
Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules.
Armour, Eric A; Carson, Robert P; Ess, Kevin C
Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia.
Cystogenesis and elongated primary cilia in Tsc1-deficient distal convoluted tubules
Armour, Eric A.; Carson, Robert P.
Tuberous sclerosis complex (TSC) is a multiorgan hamartomatous disease caused by loss of function mutations of either the TSC1 or TSC2 genes. Neurological symptoms of TSC predominate in younger patients, but renal pathologies are a serious aspect of the disease in older children and adults. To study TSC pathogenesis in the kidney, we inactivated the mouse Tsc1 gene in the distal convoluted tubules (DCT). At young ages, Tsc1 conditional knockout (CKO) mice have enlarged kidneys and mild cystogenesis with increased mammalian target of rapamycin complex (mTORC)1 but decreased mTORC2 signaling. Treatment with the mTORC1 inhibitor rapamycin reduces kidney size and cystogenesis. Rapamycin withdrawal led to massive cystogenesis involving both distal as well as proximal tubules. To assess the contribution of decreased mTORC2 signaling in kidney pathogenesis, we also generated Rictor CKO mice. These animals did not have any detectable kidney pathology. Finally, we examined primary cilia in the DCT. Cilia were longer in Tsc1 CKO mice, and rapamycin treatment returned cilia length to normal. Rictor CKO mice had normal cilia in the DCT. Overall, our findings suggest that loss of the Tsc1 gene in the DCT is sufficient for renal cystogenesis. This cytogenesis appears to be mTORC1 but not mTORC2 dependent. Intriguingly, the mechanism may be cell autonomous as well as non-cell autonomous and possibly involves the length and function of primary cilia. PMID:22674026
Cloning and chromosomal localization of the three human syntrophin genes
Energy Technology Data Exchange (ETDEWEB)
Feener, C.A.; Anderson, M.D.S.; Selig, S. [Children`s Hospital, Boston, MA (United States)] [and others
Dystrophin, the protein product the Duchenne muscular dystrophy locus, is normally found to be associated with a complex of proteins. Among these dystrophin-associated proteins are the syntrophins, a group of 59 kDa membrane-associated proteins. When the syntrophins are purified based upon their association with dystrophin, they have been shown previously to form two distinct groups, the acidic ({alpha}) and basic ({beta}) forms. Based on peptide and rodent cDNA sequences, three separate syntrophin genes have been cloned and characterized from human tissues. The predicted amino acid sequences from these cDNA reveal that these proteins are related but are distinct with respect to charge, as predicted from their biochemistry. The family consists of one acidic ({alpha}-syntrophin, analogous to mouse syntrophin-1) and two basic ({beta}{sub 1}-syntrophin; and {beta}{sub 2}-syntrophin, analogous to mouse syntrophin-2) genes. Each of the three genes are widely expressed in a variety of human tissues, but the relative abundance of the three are unique with respect to each other. {alpha}-syntrophin is expressed primarily in skeletal muscle and heart as a single transcript. {beta}{sub 1}-syntrophin is expressed widely in up to five distinct transcript sizes, and is most abundant in brain. The human chromosomal locations of the three syntrophins are currently being mapped. {beta}{sub 1}-syntrophin maps to chromosome 8q23-24 and {beta}{sub 2}-syntrophin to chromosome 16. The {alpha}-syntrophin gene will be mapped accordingly. Although all three genes are candidates for neuromuscular diseases, the predominant expression of {alpha}-syntrophin in skeletal muscle and heart makes it a strong candidate to be involved in a neuromuscular disease.
DNA Probe Pooling for Rapid Delineation of Chromosomal Breakpoints
Energy Technology Data Exchange (ETDEWEB)
Lu, Chun-Mei; Kwan, Johnson; Baumgartner, Adolf; Weier, Jingly F.; Wang, Mei; Escudero, Tomas; Munne' , Santiago; Zitzelsberger, Horst F.; Weier, Heinz-Ulrich
Structural chromosome aberrations are hallmarks of many human genetic diseases. The precise mapping of translocation breakpoints in tumors is important for identification of genes with altered levels of expression, prediction of tumor progression, therapy response, or length of disease-free survival as well as the preparation of probes for detection of tumor cells in peripheral blood. Similarly, in vitro fertilization (IVF) and preimplantation genetic diagnosis (PGD) for carriers of balanced, reciprocal translocations benefit from accurate breakpoint maps in the preparation of patient-specific DNA probes followed by a selection of normal or balanced oocytes or embryos. We expedited the process of breakpoint mapping and preparation of case-specific probes by utilizing physically mapped bacterial artificial chromosome (BAC) clones. Historically, breakpoint mapping is based on the definition of the smallest interval between proximal and distal probes. Thus, many of the DNA probes prepared for multi-clone and multi-color mapping experiments do not generate additional information. Our pooling protocol described here with examples from thyroid cancer research and PGD accelerates the delineation of translocation breakpoints without sacrificing resolution. The turnaround time from clone selection to mapping results using tumor or IVF patient samples can be as short as three to four days.
Molecular organization and chromosomal localization of 5S rDNA in Amazonian Engystomops (Anura, Leiuperidae).
Rodrigues, Débora Silva; Rivera, Miryan; Lourenço, Luciana Bolsoni
For anurans, knowledge of 5S rDNA is scarce. For Engystomops species, chromosomal homeologies are difficult to recognize due to the high level of inter- and intraspecific cytogenetic variation. In an attempt to better compare the karyotypes of the Amazonian species Engystomops freibergi and Engystomops petersi, and to extend the knowledge of 5S rDNA organization in anurans, the 5S rDNA sequences of Amazonian Engystomops species were isolated, characterized, and mapped. Two types of 5S rDNA, which were readily differentiated by their NTS (non-transcribed spacer) sizes and compositions, were isolated from specimens of E. freibergi from Brazil and E. petersi from two Ecuadorian localities (Puyo and Yasuní). In the E. freibergi karyotypes, the entire type I 5S rDNA repeating unit hybridized to the pericentromeric region of 3p, whereas the entire type II 5S rDNA repeating unit mapped to the distal region of 6q, suggesting a differential localization of these sequences. The type I NTS probe clearly detected the 3p pericentromeric region in the karyotypes of E. freibergi and E. petersi from Puyo and the 5p pericentromeric region in the karyotype of E. petersi from Yasuní, but no distal or interstitial signals were observed. Interestingly, this probe also detected many centromeric regions in the three karyotypes, suggesting the presence of a satellite DNA family derived from 5S rDNA. The type II NTS probe detected only distal 6q regions in the three karyotypes, corroborating the differential distribution of the two types of 5S rDNA. Because the 5S rDNA types found in Engystomops are related to those of Physalaemus with respect to their nucleotide sequences and chromosomal locations, their origin likely preceded the evolutionary divergence of these genera. In addition, our data indicated homeology between Chromosome 5 in E. petersi from Yasuní and Chromosomes 3 in E. freibergi and E. petersi from Puyo. In addition, the chromosomal location of the type II 5S r
The disequilibrium of nucleosomes distribution along chromosomes plays a functional and evolutionarily role in regulating gene expression
Cui, Peng; Lin, Qiang; Zhang, Lingfang; Ding, Feng; Xin, Chengqi; Zhang, Daoyong; Sun, Fanglin; Hu, Songnian; Yu, Jun
on ChIP (H3)-seq and RNA-seq, respectively. We identified a nearly consistent NO patterns among three mouse tissues-cerebrum, testis, and ESCs-and found, through clustering analysis for transcriptional activation, that the NO variations among chromosomes
Combined open proximal and stent-graft distal repair for distal arch aneurysms: an alternative to total debranching.
Zierer, Andreas; Sanchez, Luis A; Moon, Marc R
We present herein a novel, combined, simultaneous open proximal and stent-graft distal repair for complex distal aortic arch aneurysms involving the descending aorta. In the first surgical step, the transverse arch is opened during selective antegrade cerebral perfusion, and a Dacron graft (DuPont, Wilmington, DE) is positioned down the descending aorta in an elephant trunk-like fashion with its proximal free margin sutured circumferentially to the aorta just distal to the left subclavian or left common carotid artery. With the graft serving as the new proximal landing zone, subsequent endovascular repair is performed antegrade during rewarming through the ascending aorta.
Genetics Home Reference: ring chromosome 20 syndrome
... drugs. Prolonged seizure episodes known as non-convulsive status epilepticus also appear to be characteristic of ring chromosome ... K, Takahashi Y. Ring chromosome 20 and nonconvulsive status epilepticus. A new epileptic syndrome. Brain. 1997 Jun;120 ( ...
Chromosomal disorders and male infertility
Institute of Scientific and Technical Information of China (English)
Gary L Harton; Helen G Tempest
infertility in humans is surprisingly common occurring in approximately 15% of the population wishing to start a family.Despite this,the molecular and genetic factors underlying the cause of infertility remain largely undiscovered.Nevertheless,more and more genetic factors associated with infertility are being identified.This review will focus on our current understanding of the chromosomal basis of male infertility specifically:chromosomal aneuploidy,structural and numerical karyotype abnormalities and Y chromosomal microdeletions.Chromosomal aneuploidy is the leading cause of pregnancy loss and developmental disabilities in humans.Aneuploidy is predominantly maternal in origin,but concerns have been raised regarding the safety of intracytoplasmic sperm injection as infertile men have significantly higher levels of sperm aneuploidy compared to their fertile counterparts.Males with numerical or structural karyotype abnormalities are also at an increased risk of producing aneuploid sperm.Our current understanding of how sperm aneuploidy translates to embryo aneuploidy will be reviewed,as well as the application of preimplantation genetic diagnosis (PGD) in such cases.Clinical recommendations where possible will be made,as well as discussion of the use of emerging array technology in PGD and its potential applications in male infertility.
Chromosomal Abnormalities Associated With Omphalocele
Directory of Open Access Journals (Sweden)
Chih-Ping Chen
Full Text Available Fetuses with omphalocele have an increased risk for chromosomal abnormalities. The risk varies with maternal age, gestational age at diagnosis, association with umbilical cord cysts, complexity of associated anomalies, and the contents of omphalocele. There is considerable evidence that genetics contributes to the etiology of omphalocele. This article provides an overview of chromosomal abnormalities associated with omphalocele and a comprehensive review of associated full aneuploidy such as trisomy 18, trisomy 13, triploidy, trisomy 21, 45,X, 47,XXY, and 47,XXX, partial aneuploidy such as dup(3q, dup(11p, inv(11, dup(1q, del(1q, dup(4q, dup(5p, dup(6q, del(9p, dup(15q, dup(17q, Pallister-Killian syndrome with mosaic tetrasomy 12p and Miller-Dieker lissencephaly syndrome with deletion of 17p13.3, and uniparental disomy (UPD such as UPD 11 and UPD 14. Omphalocele is a prominent marker for chromosomal abnormalities. Perinatal identification of omphalocele should alert chromosomal abnormalities and familial unbalanced translocations, and prompt thorough cytogenetic investigations and genetic counseling.
We have used CHEF gel electrophoresis to screen preparations of large DNA from different Burkholderia cepacia isolates for the presence of DNA species corresponding to the linearized forms of the three chromosomes of 3.4,2.5, and 0.9 Mb identified in B. cepacia strain 17616. DNA ...
The XX sex chromosome complement in mice is associated with increased spontaneous lupus compared with XY.
Sasidhar, Manda V; Itoh, Noriko; Gold, Stefan M; Lawson, Gregory W; Voskuhl, Rhonda R
Many autoimmune diseases are characterised by a female predominance. This may be caused by sex hormones, sex chromosomes or both. This report uses a transgenic mouse model to investigate how sex chromosome complement, not confounded by differences in gonadal type, might contribute to lupus pathogenesis. Transgenic NZM2328 mice were created by deletion of the Sry gene from the Y chromosome, thereby separating genetic from gonadal sex. Survival, renal histopathology and markers of immune activation were compared in mice carrying the XX versus the XY(-) sex chromosome complement, with each genotype being ovary bearing. Mice with XX sex chromosome complement compared with XY(-) exhibited poorer survival rates and increased kidney pathology. Splenic T lymphocytes from XX mice demonstrated upregulated X-linked CD40 ligand expression and higher levels of activation markers ex vivo. Increased MMP, TGF and IL-13 production was found, while IL-2 was lower in XX mice. An accumulation of splenic follicular B cells and peritoneal marginal zone B cells was observed, coupled with upregulated costimulatory marker expression on B cells in XX mice. These data show that the XX sex chromosome complement, compared with XY(-), is associated with accelerated spontaneous lupus.
The origin of B chromosomes in yellow-necked mice (Apodemus flavicollis-Break rules but keep playing the game.
Directory of Open Access Journals (Sweden)
M Rajičić
Full Text Available B chromosomes (Bs are known for more than hundred years but their origin, structure and pattern of evolution are not well understood. In the past few years new methodological approaches, involving isolation of Bs followed by whole DNA amplification, DNA probe generation, and fluorescent in situ hybridization (FISH or the B chromosome DNA sequencing, has allowed detailed analysis of their origin and molecular structure in different species. In this study we explored the origin of Bs in the yellow-necked wood mouse, Apodemus flavicollis, using generation of microdissected DNA probes followed by FISH on metaphase chromosomes. Bs of A. flavicollis were successfully isolated and DNA was used as the template for B-specific probes for the first time. We revealed homology of DNA derived from the analyzed B chromosomes to the pericentromeric region (PR of sex chromosomes and subtelomeric region of two pairs of small autosomes, but lower homology to the rest of the Y chromosome. Moreover, all analysed Bs had the same structure regardless of their number per individual or the great geographic distance between examined populations from the Balkan Peninsula (Serbia and Eastern Europe (south region of Russia and central Belarus. Therefore, it was suggested that B chromosomes in A. flavicollis have a unique common origin from the PR of sex chromosomes, and/or similar evolutionary pattern.
early functional outcome of distal femoral fractures at kenyatta
African Journals Online (AJOL)
The leading cause was RTA, followed by falls from a height. ... Distal femoral fractures cause considerable morbidity .... as means and standard deviations. .... Anaesthesia. Spinal. 37 (80). General Anaesthesia (GA). 9 (20). Transfusion.
Subtrochanteric and Distal Femur Fractures in a Patient with ...
African Journals Online (AJOL)
This study reports the surgical management for this rare case and the treatment ... car accident and presented closed femoral shaft fracture associated with a ... to fix the distal femur fracture, enhancing the construction stability [Figures 4 and 5].
Minimally invasive percutaneous plate fixation of distal tibia fractures.
LENUS (Irish Health Repository)
Bahari, Syah
We report a series of 42 patients reviewed at a mean of 19.6 months after treatment of distal tibial and pilon fractures using the AO distal tibia locking plate with a minimally invasive percutaneous plate osteosynthesis (MIPPO) technique. Mean time to union was 22.4 weeks. All fractures united with acceptable alignment and angulation. Two cases of superficial infection were noted, with one case of deep infection. Mean SF36 score was 85 and mean AOFAS score was 90 at a mean of 19 months follow-up. We report satisfactory outcomes with the use of the AO distal tibia locking plate in treatment of unstable distal tibial fractures. Eighty-nine percent of the patients felt that they were back to their pre injury status and 95% back to their previous employment.
Surgical treatment of distal biceps tendon rupture: a case report
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Cristina N. Cozma
Full Text Available Objectives. Distal biceps tendon rupture affects the functional upperextremity movement, impairing supination and flexion strength. According to age, profession and additional risks treatment might be nonoperative or surgical. Methods. We describe the case of a 43 years old male patient who sustained an injury to his right distal biceps and was diagnosed with acute right distal biceps rupture. Surgical treatment was decided and biceps tendon was reinserted to the radius tuberosity using a combination of a cortical button fixation associated with an interference screw. Results. Postoperative functional result was favorable with no complications and with no movement limitation after one month. Conclusions. When possible, distal biceps tendon repair should be realized surgically because this permits restoring of the muscle strength to near normal levels with no loss of motion. Nerve complications are common; therefore the surgery should be realized by experienced upper extremity surgeons.
Theory on the mechanism of distal action of transcription factors: looping of DNA versus tracking along DNA
Energy Technology Data Exchange (ETDEWEB)
Murugan, R, E-mail: firstname.lastname@example.com [Department of Biotechnology, Indian Institute of Technology Madras, Chennai 600036 (India)
In this paper, we develop a theory on the mechanism of distal action of the transcription factors, which are bound at their respective cis-regulatory enhancer modules on the promoter-RNA polymerase II (PR) complexes to initiate the transcription event in eukaryotes. We consider both the looping and tracking modes of their distal communication and calculate the mean first passage time that is required for the distal interactions of the complex of enhancer and transcription factor with the PR via both these modes. We further investigate how this mean first passage time is dependent on the length of the DNA segment (L, base-pairs) that connects the cis-regulatory binding site and the respective promoter. When the radius of curvature of this connecting segment of DNA is R that was induced upon binding of the transcription factor at the cis-acting element and RNAPII at the promoter in cis-positions, our calculations indicate that the looping mode of distal action will dominate when L is such that L > 2{pi}R and the tracking mode of distal action will be favored when L < 2{pi}R. The time required for the distal action will be minimum when L = 2{pi}R where the typical value of R for the binding of histones will be R {approx} 16 bps and L {approx} 10{sup 2} bps. It seems that the free energy associated with the binding of the transcription factor with its cis-acting element and the distance of this cis-acting element from the corresponding promoter of the gene of interest is negatively correlated. Our results suggest that the looping and tracking modes of distal action are concurrently operating on the transcription activation and the physics that determines the timescales associated with the looping/tracking in the mechanism of action of these transcription factors on the initiation of the transcription event must put a selection pressure on the distribution of the distances of cis-regulatory modules from their respective promoters of the genes. The computational analysis
[Multiplicity of B microchromosomes in a Siberian population of mice Apodemus peninsulae (2n = 48 + 4-30 B chromosomes)].
Borisov, Iu M; Afanas'ev, A G; Lebedev, T T; Bochkarev, M N
Differentiation of four Siberian populations of East-Asian (Korean) field mice (Apodemus peninsulae) inhabiting the basin of the mid-stream of the Yenisei River was carried out according to the variants of the B chromosome system. A multiplicity of B microchromosomes (from 4 to 30) was found for the first time in all 26 mice from the left shore of the Yenisei River in the mid-stream area. All of them probably belong to a population with B microchromosomes. It is likely that in this population further reorganization of B microchromosomes into B macrochromosomes typical of this species does not occur. Two mice from this population had a large number of B chromosomes (26) earlier not observed in this species. In one mouse, the modal number of B microchromosomes was 30. This is a new maximum number of B chromosomes in this mouse species.
Genetics Home Reference: distal 18q deletion syndrome
... 18q deletion syndrome chromosome 18q monosomy chromosome 18q- syndrome De Grouchy syndrome del(18q) syndrome monosomy 18q Related Information How ... MS, Tienari PJ, Wirtavuori KO, Valanne LK. 18q-syndrome: brain MRI shows poor differentiation of gray and white matter on ... RL, Hale DE, Rose SR, Leach RJ, Cody JD. The spectrum ...
New distal marker closely linked to the fragile X locus
Hulsebos, T. J.; Oostra, B. A.; Broersen, S.; Smits, A.; van Oost, B. A.; Westerveld, A.
We have isolated II-10, a new X-chromosomal probe that identifies a highly informative two-allele TaqI restriction fragment length polymorphism at locus DXS466. Using somatic cell hybrids containing distinct portions of the long arm of the X chromosome, we could localize DXS466 between DXS296 and
Enclavado endomedular en fracturas del tercio distal de la tibia
Arroquy, Damian; Chahla, Jorge; Gomez Rodriguez, Gustavo; Cid Casteulani, Alberto; Svarzchtein, Santiago; Gomez, Diego; Pesciallo, Cesar
Objetivo: Describir los resultados obtenidos con el enclavado endomedular acerrojado en pacientes con fractura del tercio distal de la tibia. Materiales y Métodos: Se incluyeron pacientes con fracturas desplazadas del tercio distal de la tibia, tratadas con clavo endomedular. La muestra incluyo 35 pacientes. El tiempo de seguimiento posoperatorio fue de 29.2 meses. Se evaluaron el tiempo de consolidacion, la consolidacion viciosa y las complicaciones. Los resultados funcionales se determinaro...
Fractures of the Distal Tibia Treated with Polyaxial Locking Plating
Gao, Hong; Zhang, Chang-Qing; Luo, Cong-Feng; Zhou, Zu-Bin; Zeng, Bing-Fang
We evaluated the healing rate, complications, and functional outcomes in 32 adult patients with very short metaphyseal fragments in fractures of the distal tibia treated with a polyaxial locking system. The average distance from the distal extent of the fracture to the tibial plafond was 11 mm. All fractures healed and the average time to union was 14 weeks. Six patients (19%) reported occasional local disturbance over the medial malleolus. There were two cases of postoperative superficial in...
Interleukin 3 gene is located on human chromosome 5 and is deleted in myeloid leukemias with a deletion of 5q
International Nuclear Information System (INIS)
Le Beau, M.M.; Epstein, N.D.; O'Brien, S.J.; Nienhuis, A.W.; Yang, Y.C.; Clark, S.C.; Rowley, J.D.
The gene IL-3 encodes interleukin 3, a hematopoietic colony-stimulating factor (CSF) that is capable of supporting the proliferation of a broad range of hematopoietic cell types. By using somatic cell hybrids and in situ chromosomal hybridization, the authors localized this gene to human chromosome 5 at bands q23-31, a chromosomal region that is frequently deleted [del(5q)] in patients with myeloid disorders. By in situ hybridization, IL-3 was found to be deleted in the 5q-chromosome of one patient with refractory anemia who had a del(5)(q15q33.3), of three patients with refractory anemia (two patients) or acute nonlymphocytic leukemia (ANLL) de novo who had a similar distal breakpoint [del(5)(q13q33.3)], and of a fifth patient, with therapy-related ANLL, who had a similar distal breakpoint in band q33[del(5)(q14q33.3)]. Southern blot analysis of somatic cell hybrids retaining the normal or the deleted chromosome 5 from two patients with the refractory anemia 5q- syndrome indicated that IL-3 sequences were absent from the hybrids retaining the deleted chromosome 5 but not from hybrids that had a cytologically normal chromosome 5. Thus, a small segment of chromosome 5 contains IL-3, GM-CSF, CSF-1, and FMS. The findings and earlier results indicating that GM-CSF, CSF-1, and FMS were deleted in the 5q- chromosome, suggest that loss of IL-3 or of other CSF genes may play an important role in the pathogenesis of hematologic disorders associated with a del(5q)
Mapping of the Mouse Actin Capping Protein Beta Subunit Gene
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Cooper John A
Full Text Available Abstract Background Capping protein (CP, a heterodimer of α and β subunits, is found in all eukaryotes. CP binds to the barbed ends of actin filaments in vitro and controls actin assembly and cell motility in vivo. Vertebrates have three isoforms of CPβ produced by alternatively splicing from one gene; lower organisms have one gene and one isoform. Results We isolated genomic clones corresponding to the β subunit of mouse CP and identified its chromosomal location by interspecies backcross mapping. Conclusions The CPβ gene (Cappb1 mapped to Chromosome 4 between Cdc42 and D4Mit312. Three mouse mutations, snubnose, curly tail, and cribriform degeneration, map in the vicinity of the β gene.
High-Resolution Maps of Mouse Reference Populations
Czech Academy of Sciences Publication Activity Database
Šimeček, Petr; Forejt, Jiří; Williams, R. W.; Shiroishi, T.; Takada, T.; Lu, L.; Johnson, T. E.; Bennett, B.; Deschepper, C. F.; Scott-Boyer, M.P.; de Villena, F.P.M.; Churchill, G. A.
Roč. 7, č. 10 (2017), s. 3427-3434 ISSN 2160-1836 R&D Projects: GA ČR GA16-01969S; GA MŠk(CZ) LM2015040; GA MŠk(CZ) LQ1604 Institutional support: RVO:68378050 Keywords : chromosome substitution strains * recombinant inbred strains * mouse diversity genotyping array * gene conversions Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 2.861, year: 2016
Cytogenetics of Post-Irradiation Mouse Leukaemia
Energy Technology Data Exchange (ETDEWEB)
Wald, N.; Pan, S.; Upton, A.; Brown, R. [Graduate School of Public Health, University of Pittsburgh, PA (United States); Oak Ridge National Laboratory, Oak Ridge, TN (United States)
The interrelationship between radiation, cytogenetic abnormalities, and viruses in leukaemogenesis has been studied in the RF/Un mouse which develops a high incidence of granulocytic leukaemia on radiation exposure. A virus-like agent has been demonstrated in such leukaemic animals and the disease has been transmitted by passage of apparently acellular materials from irradiated primary animals to normal recipients. Pilot cytogenetic studies revealed consistent abnormal chromosome markers and modal shifts in both irradiated leukaemic animals and in non-irradiated animals developing leukaemia after passage injection. To define better the relationship between consistent bone-marrow chromosome aberrations and postirradiation primary and passaged leukaemia, 100 RF/Un mice were studied which were irradiated with 300 R of 250-kVp X-rays at 100 weeks of age and subsequently developed leukaemia. Eighty-seven had granulocytic leukaemia and in 72 of these, bone-marrow cytogenetic abnormalities were found. The distribution of-numerical and structural chromosome aberrations in 3225 cells studied are reviewed in derail. The correlation of specific aberrations to clinical and histopathologic findings has been attempted: Sequential passages of apparently cell-free material from the post-irradiation leukaemic mice into unirradiated RE/Un recipients and subsequent passages from leukaemic recipients were performed to observe the evolution of any initial chromosome markers and shifts in modal chromosome number in the passage generations. Two-hundred-thirty-six mice were inoculated with the material obtained either from primary post-irradiation leukaemic mice or from serially-passaged leukaemia cases. In the most extensive passaged line, 22 transfer generations containing 129 leukaemic mice were examined by clinical, histopathologic, -haematologic and cytogenetic procedures. Evolution of abnormal chromosome modes from 41 in the early passages to 39 chromosomes consistently after the 4
The role of imaging in diagnosing diseases of the distal radioulnar joint, triangular fibrocartilage complex, and distal ulna.
Squires, Judy H; England, Eric; Mehta, Kaushal; Wissman, Robert D
The purpose of this article is to review the anatomy, biomechanics, and multimodality imaging findings of common and uncommon distal radioulnar joint (DRUJ), triangular fibrocartilage complex, and distal ulna abnormalities. The DRUJ is a common site for acute and chronic injuries and is frequently imaged to evaluate chronic wrist pain, forearm dysfunction, and traumatic forearm injury. Given the complex anatomy of the wrist, the radiologist plays a vital role in the diagnosis of wrist pain and dysfunction.
Chromosomal Evolution in Lower Vertebrates: Sex Chromosomes in Neotropical Fishes
Czech Academy of Sciences Publication Activity Database
Cioffi, M. de B.; Yano, C. F.; Sember, Alexandr; Bertollo, L.A.C.
Roč. 8, č. 10 (2017), č. článku 258. ISSN 2073-4425 R&D Projects: GA MŠk EF15_003/0000460 Institutional support: RVO:67985904 Keywords : alternative evolutionary models * simple and multiple sex chromosomes * independent and common origins Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 3.600, year: 2016
Flow cytogenetic studies in chromosomes and whole cells for the detection of clastogenic effects
International Nuclear Information System (INIS)
Otto, F.J.; Oldiges, H.
Flow cytometric measurements of the chromosomal DNA content have been used to develop a screening method for the detection of chemically- or physically-induced cytogenetic damage. The reproducibility of this flow cytogenetic assay was shown in a series of subcultures of a Chinese hamster cell clone. The accuracy and sensitivity was tested in cultures treated with chemical mutagens and x-rays. The clastogenic effectiveness was quantified and the dose-effect relationship was established by the increase of the coefficient of variation of the peak of the largest chromosome type in the flow histograms. Since structural chromosome aberrations cause an unequal division of the DNA at mitosis, it is expected that clastogenic effects can be detected also in whole cells of growing populations as an increased dispersion of the cellular DNA content. In order to test this feature, high resolution flow cytometric measurements were performed in x-irradiated hamster cells in vitro and mouse bone marrow cells in vivo
Transfer of stem cells carrying engineered chromosomes with XY clone laser system.
Sinko, Ildiko; Katona, Robert L
Current transgenic technologies for gene transfer into the germline of mammals cause a random integration of exogenous naked DNA into the host genome that can generate undesirable position effects as well as insertional mutations. The vectors used to generate transgenic animals are limited by the amount of foreign DNA they can carry. Mammalian artificial chromosomes have large DNA-carrying capacity and ability to replicate in parallel with, but without integration into, the host genome. Hence they are attractive vectors for transgenesis, cellular protein production, and gene therapy applications as well. ES cells mediated chromosome transfer by conventional blastocyst injection has a limitation in unpredictable germline transmission. The demonstrated protocol of laser-assisted microinjection of artificial chromosome containing ES cells into eight-cell mouse embryos protocol described here can solve the problem for faster production of germline transchromosomic mice.
Microdissection and Chromosome Painting of the Alien Chromosome in an Addition Line of Wheat - Thinopyrum intermedium
Yin, Weibo; Zhang, Yingxin; Chen, Yuhong; Wang, Richard R.-C.; Zhang, Xiangqi; Han, Fangpu; Hu, Zanmin
In this study, chromosome painting was developed and used to identify alien chromosomes in TAi-27, a wheat - Thinopyrum intermedium addition line, and the chromosomes of the three different genomes of Th. Intermedium. The smallest alien chromosome of TAi-27 was microdissected and its DNA amplified by DOP-PCR was used as a probe to hybridize with metaphase chromosomes of TAi-27 and Th . intermedium . Results showed that hybridization signals were observed in all regions of a pair of the smallest alien chromosomes and the pericentromeric area of another pair of alien chromosomes in TAi-27, indicating that the probe from microdissected chromosome is species specific. In Th . intermedium , 14 chromosomes had wide and strong hybridization signals distributed mainly on the pericentromere area and 9 chromosomes with narrow and weak signals on the pericentromere area. The remaining chromosomes displayed a very weak or no signal. Sequential FISH/GISH on Th . intermedium chromosomes using the DNAs of microdissected chromosome, Pseudoroegneria spicata (St genome) and pDbH12 (a Js genome specific probe) as the probes indicated that the microdissected chromosome belonged to the St genome, three genomes (Js, J and St) in Th . intermedium could be distinguished, in which there is no hybridization signal on J genome that is similar to the genome of Th . bessarabicum . Our results showed that the smallest alien chromosomes may represent a truncated chromosome and the repetitive sequence distribution might be similar in different chromosomes within the St genome. However, the repetitive sequence distributions are different within the Js genome, within a single chromosome, and among different genomes in Th . intermedium . Our results suggested that chromosome painting could be feasible in some plants and useful in detecting chromosome variation and repetitive sequence distribution in different genomes of polyploidy plants, which is helpful for understanding the evolution of different
Telomere-mediated chromosomal instability triggers TLR4 induced inflammation and death in mice.
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Rabindra N Bhattacharjee
Full Text Available BACKGROUND: Telomeres are essential to maintain chromosomal stability. Cells derived from mice lacking telomerase RNA component (mTERC-/- mice display elevated telomere-mediated chromosome instability. Age-dependent telomere shortening and associated chromosome instability reduce the capacity to respond to cellular stress occurring during inflammation and cancer. Inflammation is one of the important risk factors in cancer progression. Controlled innate immune responses mediated by Toll-like receptors (TLR are required for host defense against infection. Our aim was to understand the role of chromosome/genome instability in the initiation and maintenance of inflammation. METHODOLOGY/PRINCIPAL FINDINGS: We examined the function of TLR4 in telomerase deficient mTERC-/- mice harbouring chromosome instability which did not develop any overt immunological disorder in pathogen-free condition or any form of cancers at this stage. Chromosome instability was measured in metaphase spreads prepared from wildtype (mTERC+/+, mTERC+/- and mTERC-/- mouse splenocytes. Peritoneal and/or bone marrow-derived macrophages were used to examine the responses of TLR4 by their ability to produce inflammatory mediators TNFalpha and IL6. Our results demonstrate that TLR4 is highly up-regulated in the immune cells derived from telomerase-null (mTERC-/- mice and lipopolysaccharide, a natural ligand for TLR4 stabilises NF-kappaB binding to its promoter by down-regulating ATF-3 in mTERC-/- macrophages. CONCLUSIONS/SIGNIFICANCE: Our findings implied that background chromosome instability in the cellular level stabilises the action of TLR4-induced NF-kappaB action and sensitises cells to produce excess pro-inflammatory mediators. Chromosome/genomic instability data raises optimism for controlling inflammation by non-toxic TLR antagonists among high-risk groups.
Volar plating for distal radius fractures--do not trust the image intensifier when judging distal subchondral screw length.
Park, Derek H; Goldie, Boyd S
The use of the volar plate to treat distal radius fractures is increasing but despite the theoretical advantages of a volar approach there have been reports of extensor tendon ruptures due to prominent screw tips protruding past the dorsal cortex. The valley in the intermediate column between Lister tubercle and the sigmoid notch of the distal radius makes it difficult to rely on fluoroscopy to judge screw length. Our aim was to quantify the dimensions of this valley and to demonstrate the danger of relying on intraoperative image intensification fluoroscopy to determine lengths of distal screws. We measured the depth of this valley in the intermediate column of the distal radius in 33 patients with computed tomographic (9 patients) or magnetic resonance image (24 patients) scans of the wrist. There was a consistent valley in all images examined [average 1.8 mm (95% confidence interval, 1.6-2.0 mm)]. Thirty-nine percent of wrists had a valley depth of at least 2 mm. Standard lateral views or rotation of the forearm to obtain oblique views does not identify prominent screw tips; and whatever the rotation of the forearm, screw tips protruding beyond dorsal cortex may look as if it is within the bone when in fact it is out. When drilling we suggest noting the depth at which the drill bit just penetrates dorsal cortex and routinely downsize the distal screw length by 2 mm. We caution against relying on flourosocopy when judging the length of the distal subchondral screws.
Odf2-deficient mother centrioles lack distal/subdistal appendages and the ability to generate primary cilia.
Ishikawa, Hiroaki; Kubo, Akiharu; Tsukita, Shoichiro; Tsukita, Sachiko
Outer dense fibre 2 (Odf2; also known as cenexin) was initially identified as a main component of the sperm tail cytoskeleton, but was later shown to be a general scaffold protein that is specifically localized at the distal/subdistal appendages of mother centrioles. Here we show that Odf2 expression is suppressed in mouse F9 cells when both alleles of Odf2 genes are deleted. Unexpectedly, the cell cycle of Odf2(-/-) cells does not seem to be affected. Immunofluorescence and ultrathin-section electron microscopy reveals that in Odf2(-/-) cells, distal/subdistal appendages disappear from mother centrioles, making it difficult to distinguish mother from daughter centrioles. In Odf2(-/-) cells, however, the formation of primary cilia is completely suppressed, although approximately 25% of wild-type F9 cells are ciliated under the steady-state cell cycle. The loss of primary cilia in Odf2(-/-) F9 cells can be rescued by exogenous Odf2 expression. These findings indicate that Odf2 is indispensable for the formation of distal/subdistal appendages and the generation of primary cilia, but not for other cell-cycle-related centriolar functions.
Hereditary spastic paraplegia and amyotrophy associated with a novel locus on chromosome 19
Meilleur, K.G.; Traoré, M.; Sangaré, M.; Britton, A.; Landouré, G.; Coulibaly, S.; Niaré, B.; Mochel, F.; La Pean, A.; Rafferty, I.; Watts, C.; Littleton-Kearney, M. T.; Blackstone, C.; Singleton, A.; Fischbeck, K.H.
We identified a family in Mali with two sisters affected by spastic paraplegia. In addition to spasticity and weakness of the lower limbs, the patients had marked atrophy of the distal upper extremities. Homozygosity mapping using single nucleotide polymorphism arrays showed that the sisters shared a region of extended homozygosity at chromosome 19p13.11-q12 that was not shared by controls. These findings indicate a clinically and genetically distinct form of hereditary spastic paraplegia with amyotrophy, designated SPG43. PMID:20039086
Dynamics of chromosome segregation in Escherichia coli
DEFF Research Database (Denmark)
Nielsen, Henrik Jørck
Since the 1960'es the conformation and segregation of the chromosome in Escherichia coli has been a subject of interest for many scientists. However, after 40 years of research, we still know incredibly little about how the chromosome is organized inside the cell, how it manages to duplicate...... this incredibly big molecule and separate the two daughter chromosomes and how it makes sure that the daughter cells receives one copy each. The fully extended chromosome is two orders of magnitude larger than the cell in which it is contained. Hence the chromosome is heavily compacted in the cell...
A chromosome study of 6-thioguanine-resistant mutants in T lymphocytes of Hiroshima atomic bomb survivors
International Nuclear Information System (INIS)
Kodama, Yoshiaki; Hakoda, Masayuki; Shimba, Hachiro; Awa, A.A.; Akiyama, Mitoshi.
Cytogenetic characterizations were made of lymphocyte colonies established from somatic mutation assays for 6-thioguanine (TG) resistance in Hiroshima atomic bomb survivors. G-banded chromosomes were analyzed in both TG-resistant (TG r ) and wild-type (not TG-selected) colonies. Included were 45 TG r and 19 wild-type colonies derived from proximally exposed A-bomb survivors, as well as colonies from distally exposed control individuals who were not exposed to a significant level of A-bomb radiation (18 TG r and 9 wild-type colonies). Various structural and numerical abnormalities of chromosomes were observed in both TG r and wild-type colonies. Aberrations of the X chromosome, on which the hypoxanthine guanine phosphoribosyltransferase (HPRT) locus is present, were found in six colonies: two resistant colonies from controls [45,X/46,XX; 46,X,ins(X)], three resistant colonies [45,X/46,XX/46,X,+mar; 46,X,t(Xq+;14q-); 46,Y,t(Xq-;5q+)], and one wild-type colony [45,X/47,XXX] from proximally exposed persons. In cases with exchange aberrations, each of the break points on the X chromosome was situated proximally to band q26 where the HPRT locus is known to be assigned. DNA replicating patterns were also studied, and it was found that abnormal X chromosomes showed early replicating patterns, while normal X chromosomes showed late replicating patterns. (author)
Conversion and non-conversion approach to preimplantation diagnosis for chromosomal rearrangements in 475 cycles.
Kuliev, Anver; Janzen, Jeanine Cieslak; Zlatopolsky, Zev; Kirillova, Irina; Ilkevitch, Yury; Verlinsky, Yury
Due to the limitations of preimplantation genetic diagnosis (PGD) for chromosomal rearrangements by interphase fluorescent in-situ hybridization (FISH) analysis, a method for obtaining chromosomes from single blastomeres was introduced by their fusion with enucleated or intact mouse zygotes, followed by FISH analysis of the resulting heterokaryons. Although this allowed a significant improvement in the accuracy of testing of both maternally and paternally derived translocations, it is still labour intensive and requires the availability of fertilized mouse oocytes, also creating ethical issues related to the formation of interspecies heterokaryons. This method was modified with a chemical conversion procedure that has now been clinically applied for the first time on 877 embryos from PGD cycles for chromosomal rearrangements and has become the method of choice for performing PGD for structural rearrangements. This is presented within the context of overall experience of 475 PGD cycles for translocations with pre-selection and transfer of balanced or normal embryos in 342 (72%) of these cycles, which resulted in 131 clinical pregnancies (38%), with healthy deliveries of 113 unaffected children. The spontaneous abortion rate in these cycles was as low as 17%, which confirms an almost five-fold reduction of spontaneous abortion rate following PGD for chromosomal rearrangements. 2010 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.
Small chromosomal regions position themselves autonomously according to their chromatin class.
van de Werken, Harmen J G; Haan, Josien C; Feodorova, Yana; Bijos, Dominika; Weuts, An; Theunis, Koen; Holwerda, Sjoerd J B; Meuleman, Wouter; Pagie, Ludo; Thanisch, Katharina; Kumar, Parveen; Leonhardt, Heinrich; Marynen, Peter; van Steensel, Bas; Voet, Thierry; de Laat, Wouter; Solovei, Irina; Joffe, Boris
The spatial arrangement of chromatin is linked to the regulation of nuclear processes. One striking aspect of nuclear organization is the spatial segregation of heterochromatic and euchromatic domains. The mechanisms of this chromatin segregation are still poorly understood. In this work, we investigated the link between the primary genomic sequence and chromatin domains. We analyzed the spatial intranuclear arrangement of a human artificial chromosome (HAC) in a xenospecific mouse background in comparison to an orthologous region of native mouse chromosome. The two orthologous regions include segments that can be assigned to three major chromatin classes according to their gene abundance and repeat repertoire: (1) gene-rich and SINE-rich euchromatin; (2) gene-poor and LINE/LTR-rich heterochromatin; and (3) gene-depleted and satellite DNA-containing constitutive heterochromatin. We show, using fluorescence in situ hybridization (FISH) and 4C-seq technologies, that chromatin segments ranging from 0.6 to 3 Mb cluster with segments of the same chromatin class. As a consequence, the chromatin segments acquire corresponding positions in the nucleus irrespective of their chromosomal context, thereby strongly suggesting that this is their autonomous property. Interactions with the nuclear lamina, although largely retained in the HAC, reveal less autonomy. Taken together, our results suggest that building of a functional nucleus is largely a self-organizing process based on mutual recognition of chromosome segments belonging to the major chromatin classes. © 2017 van de Werken et al.; Published by Cold Spring Harbor Laboratory Press.
Neurogenin 3 Mediates Sex Chromosome Effects on the Generation of Sex Differences in Hypothalamic Neuronal Development
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Maria Julia Scerbo
Full Text Available The organizational action of testosterone during critical periods of development is the cause of numerous sex differences in the brain. However, sex differences in neuritogenesis have been detected in primary neuronal hypothalamic cultures prepared before the peak of testosterone production by fetal testis. In the present study we assessed the hypothesis of that cell-autonomous action of sex chromosomes can differentially regulate the expression of the neuritogenic gene neurogenin 3 (Ngn3 in male and female hypothalamic neurons, generating sex differences in neuronal development. Neuronal cultures were prepared from male and female E14 mouse hypothalami, before the fetal peak of testosterone. Female neurons showed enhanced neuritogenesis and higher expression of Ngn3 than male neurons. The silencing of Ngn3 abolished sex differences in neuritogenesis, decreasing the differentiation of female neurons. The sex difference in Ngn3 expression was determined by sex chromosomes, as demonstrated using the four core genotypes mouse model, in which a spontaneous deletion of the testis-determining gene Sry from the Y chromosome was combined with the insertion of the Sry gene onto an autosome. In addition, the expression of Ngn3, which is also known to mediate the neuritogenic actions of estradiol, was increased in the cultures treated with the hormone, but only in those from male embryos. Furthermore, the hormone reversed the sex differences in neuritogenesis promoting the differentiation of male neurons. These findings indicate that Ngn3 mediates both cell-autonomous actions of sex chromosomes and hormonal effects on neuritogenesis.
ATM promotes the obligate XY crossover and both crossover control and chromosome axis integrity on autosomes.
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Marco Barchi
Full Text Available During meiosis in most sexually reproducing organisms, recombination forms crossovers between homologous maternal and paternal chromosomes and thereby promotes proper chromosome segregation at the first meiotic division. The number and distribution of crossovers are tightly controlled, but the factors that contribute to this control are poorly understood in most organisms, including mammals. Here we provide evidence that the ATM kinase or protein is essential for proper crossover formation in mouse spermatocytes. ATM deficiency causes multiple phenotypes in humans and mice, including gonadal atrophy. Mouse Atm-/- spermatocytes undergo apoptosis at mid-prophase of meiosis I, but Atm(-/- meiotic phenotypes are partially rescued by Spo11 heterozygosity, such that ATM-deficient spermatocytes progress to meiotic metaphase I. Strikingly, Spo11+/-Atm-/- spermatocytes are defective in forming the obligate crossover on the sex chromosomes, even though the XY pair is usually incorporated in a sex body and is transcriptionally inactivated as in normal spermatocytes. The XY crossover defect correlates with the appearance of lagging chromosomes at metaphase I, which may trigger the extensive metaphase apoptosis that is observed in these cells. In addition, control of the number and distribution of crossovers on autosomes appears to be defective in the absence of ATM because there is an increase in the total number of MLH1 foci, which mark the sites of eventual crossover formation, and because interference between MLH1 foci is perturbed. The axes of autosomes exhibit structural defects that correlate with the positions of ongoing recombination. Together, these findings indicate that ATM plays a role in both crossover control and chromosome axis integrity and further suggests that ATM is important for coordinating these features of meiotic chromosome dynamics.
Arthroplasty of the distal ulna distal in managing patients with post-traumatic disorders of the distal radioulnar joint: measurement of quality of life
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Marcio Aurélio Aita
Full Text Available ABSTRACT OBJECTIVE: To measure the quality of life and clinical-functional results from patients diagnosed with osteoarthrosis of the distal radioulnar joint who underwent surgical treatment using the technique of total arthroplasty of the ulna, with a total or partial Ascension(r prosthesis of the distal ulna. METHODS: Ten patients were evaluated after 12 months of follow-up subsequent to total or partial arthroplasty of the distal ulna. All of them presented post-traumatic osteoarthrosis and/or chronic symptomatic instability of the distal radioulnar joint. The study was prospective. Seven patients had previously undergone wrist procedures (two cases with Darrach, three with Sauvé-Kapandji and two with ligament reconstruction of the fibrocartilage complex and three presented fractures of the distal ulna that evolved with pain, instability and osteoarthrosis of the distal radioulnar joint. The following were assessed: quality of life (DASH scale; percentage degree of palm grip strength (kgf and pronosupination range of motion in relation to the unaffected side; pain (VAS; return to work; subjective evaluation of radiography; and complications. RESULTS: The patients presented a mean range of motion of 174.5° (normal side: 180°. Quality of life was analyzed by applying the DASH questionnaire and the mean value found was 5.9. The mean pain score using the VAS was 2.3. The mean degree of palm grip strength (kgf was 50.7, which represented 90.7% of the strength on the unaffected side. The complication rate was 10%: this patient presented slight dorsal instability of the ulna and persistent pain, and did not return to work. This patient is still being followed up in the outpatient clinic and occupational therapy sector, with little improvement. He does not wish to undergo a new procedure. The mean length of follow-up was 16.8 months, with a minimum of 10 and maximum of 36 months. CONCLUSION: This concept is subject to the test of time
Frequencies of chromosome aberration on radiation workers
International Nuclear Information System (INIS)
Yanti Lusiyanti; Zubaidah Alatas
Radiation exposure of the body can cause damage to the genetic material in cells (cytogenetic) in the form of changes in the structure or chromosomal aberrations in peripheral blood lymphocytes. Chromosomal aberrations can be unstable as dicentric and ring chromosomes, and is stable as translocation. Dicentric chromosome is the gold standard biomarker due to radiation exposure, and chromosome translocation is a biomarker for retrospective biodosimetry. The aim of this studi is to conduct examination of chromosomal aberrations in the radiation worker to determine the potential damage of cell that may arise due to occupational radiation exposure. The examination have been carried out on blood samples from 55 radiation workers in the range of 5-30 year of service. Chromosome aberration frequency measurement starts with blood sampling, culturing, harvesting, slide preparations, and lymphocyte chromosome staining with Giemsa and painting with Fluorescence In Situ Hybridization (FISH) technique. The results showed that chromosomal translocations are not found in blood samples radiation workers and dicentric chromosomes found only on 2 blood samples of radiation workers with a frequency of 0.001/cell. The frequency of chromosomal aberrations in the blood cells such workers within normal limits and this means that the workers have been implemented a radiation safety aspects very well. (author)
Chromosomal instability induced by ionizing radiation
International Nuclear Information System (INIS)
Morgan, W.F.; Marder, B.A.; Day, J.P.
There is accumulating evidence indicating genomic instability can manifest multiple generations after cellular exposure to DNA damaging agents. For instance, some cells surviving exposure to ionizing radiations show delayed reproductive cell death, delayed mutation and / or delayed chromosomal instability. Such instability, especially chromosome destabilization has been implicated in mutation, gene amplification, cellular transformation, and cell killing. To investigate chromosomal instability following DNA damage, we have used fluorescence in situ hybridization to detect chromosomal rearrangements in a human/hamster somatic hybrid cell line following exposure to ionizing radiation. Delayed chromosomal instability was detected when multiple populations of uniquely arranged metaphases were observed in clonal isolates raised from single cells. The relationship between delayed chromosomal destabilization and other endpoints of genomic instability, namely; delayed mutation and gene amplification will be discussed, as will the potential cytogenetic and molecular mechanisms contributing to delayed chromosomal instability
Delayed chromosomal instability induced by DNA damage
International Nuclear Information System (INIS)
Morgan, W.F.; Marder, B.A.; Day, J.P.
Cellular exposure to DNA damaging agents rapidly results in a dose dependent increase in chromosomal breakage and gross structural chromosomal rearrangements. Over recent years, evidence has been accumulating indicating genomic instability can manifest multiple generations after cellular exposure to physical and chemical DNA damaging agents. Genomic instability manifests in the progeny of surviving cells, and has been implicated in mutation, gene application, cellular transformation, and cell killing. To investigate chromosome instability following DNA damage, we have used fluorescence in situ hybridization to detect chromosomal rearrangements in a human/hamster somatic hybrid cell line following exposure to ionizing radiation. Delayed chromosomal instability was detected when multiple populations of uniquely arranged metaphases were observed in clonal isolates raised from single cells surviving X-irradiation many generations after exposure. At higher radiation doses, chromosomal instability was observed in a relatively high frequency of surviving clones and, in general, those clones showed delayed chromosome instability also showed reduced survival as measured by colony forming ability
Genome Organization Drives Chromosome Fragility.
Canela, Andres; Maman, Yaakov; Jung, Seolkyoung; Wong, Nancy; Callen, Elsa; Day, Amanda; Kieffer-Kwon, Kyong-Rim; Pekowska, Aleksandra; Zhang, Hongliang; Rao, Suhas S P; Huang, Su-Chen; Mckinnon, Peter J; Aplan, Peter D; Pommier, Yves; Aiden, Erez Lieberman; Casellas, Rafael; Nussenzweig, André
In this study, we show that evolutionarily conserved chromosome loop anchors bound by CCCTC-binding factor (CTCF) and cohesin are vulnerable to DNA double strand breaks (DSBs) mediated by topoisomerase 2B (TOP2B). Polymorphisms in the genome that redistribute CTCF/cohesin occupancy rewire DNA cleavage sites to novel loop anchors. While transcription- and replication-coupled genomic rearrangements have been well documented, we demonstrate that DSBs formed at loop anchors are largely transcription-, replication-, and cell-type-independent. DSBs are continuously formed throughout interphase, are enriched on both sides of strong topological domain borders, and frequently occur at breakpoint clusters commonly translocated in cancer. Thus, loop anchors serve as fragile sites that generate DSBs and chromosomal rearrangements. VIDEO ABSTRACT. Published by Elsevier Inc.
Chromosomes aberations and enviromental factors
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Marković Srđan Z.
Full Text Available Explanation the topic: Changes in genetic material can lead to aberrant cell in the direction of disorders of cellular regulation, malignant transformation, cell death, or if the adjustment was made at the level of the reproductive cells, to genetic changes in some of the consequent off spring. The topic position in scientific/professional public: Breaking of chromosomes can occur spontaneously or can be induced. Chromatid/chromosome breakings can be induced by different environmental factors: chemicals, biological clastogenic agents, accidentally or intentionally. Conclusions: The authors suggest: - making conditions for strong respect of environmental regulations; - to use higher plants for the early detection of environmental mutagens; - create and orderly update National radionuclide database.
Sexual dimorphism in mammalian autosomal gene regulation is determined not only by Sry but by sex chromosome complement as well.
Wijchers, Patrick J; Yandim, Cihangir; Panousopoulou, Eleni; Ahmad, Mushfika; Harker, Nicky; Saveliev, Alexander; Burgoyne, Paul S; Festenstein, Richard
Differences between males and females are normally attributed to developmental and hormonal differences between the sexes. Here, we demonstrate differences between males and females in gene silencing using a heterochromatin-sensitive reporter gene. Using "sex-reversal" mouse models with varying sex chromosome complements, we found that this differential gene silencing was determined by X chromosome complement, rather than sex. Genome-wide transcription profiling showed that the expression of hundreds of autosomal genes was also sensitive to sex chromosome complement. These genome-wide analyses also uncovered a role for Sry in modulating autosomal gene expression in a sex chromosome complement-specific manner. The identification of this additional layer in the establishment of sexual dimorphisms has implications for understanding sexual dimorphisms in physiology and disease. Copyright © 2010 Elsevier Inc. All rights reserved.
Inducible protective processes in animal systems XIV: Cytogenetic adaptive response induced by EMS or MMS in bone marrow cells of diabetic mouse
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B.B. Dada Khalandar
Conclusion: (1 Methylating agents are a more effective inducer of adaptive response than ethylating agents in diabetic mouse. (2 Further, it is interesting to note that the percentage reduction of chromosomal breaks in diabetics is comparatively much less than in non diabetic mouse, inferring that there is variation in adaptive response between diseased and non diseased condition.
Microdissection and chromosome painting of the alien chromosome in an addition line of wheat-Thinopyrum intermedium
The chromosome painting is an efficient tool for chromosome research. However, plant chromosome painting is relatively underdeveloped. In this study, chromosome painting was developed and used to identify alien chromosomes in TAi-27, a wheat-Thinopyrum intermedium addition line, and chromosomes of...
GSK-3 inhibitors induce chromosome instability
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Staples Oliver D
Full Text Available Abstract Background Several mechanisms operate during mitosis to ensure accurate chromosome segregation. However, during tumour evolution these mechanisms go awry resulting in chromosome instability. While several lines of evidence suggest that mutations in adenomatous polyposis coli (APC may promote chromosome instability, at least in colon cancer, the underlying mechanisms remain unclear. Here, we turn our attention to GSK-3 – a protein kinase, which in concert with APC, targets β-catenin for proteolysis – and ask whether GSK-3 is required for accurate chromosome segregation. Results To probe the role of GSK-3 in mitosis, we inhibited GSK-3 kinase activity in cells using a panel of small molecule inhibitors, including SB-415286, AR-A014418, 1-Azakenpaullone and CHIR99021. Analysis of synchronised HeLa cells shows that GSK-3 inhibitors do not prevent G1/S progression or cell division. They do, however, significantly delay mitotic exit, largely because inhibitor-treated cells have difficulty aligning all their chromosomes. Although bipolar spindles form and the majority of chromosomes biorient, one or more chromosomes often remain mono-oriented near the spindle poles. Despite a prolonged mitotic delay, anaphase frequently initiates without the last chromosome aligning, resulting in chromosome non-disjunction. To rule out the possibility of "off-target" effects, we also used RNA interference to selectively repress GSK-3β. Cells deficient for GSK-3β exhibit a similar chromosome alignment defect, with chromosomes clustered near the spindle poles. GSK-3β repression also results in cells accumulating micronuclei, a hallmark of chromosome missegregation. Conclusion Thus, not only do our observations indicate a role for GSK-3 in accurate chromosome segregation, but they also raise the possibility that, if used as therapeutic agents, GSK-3 inhibitors may induce unwanted side effects by inducing chromosome instability.
Chromosome aberration assays in Allium
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Grant, W.F.
The common onion (Allium cepa) is an excellent plant for the assay of chromosome aberrations after chemical treatment. Other species of Allium (A. cepa var. proliferum, A. carinatum, A. fistulosum and A. sativum) have also been used but to a much lesser extent. Protocols have been given for using root tips from either bulbs or seeds of Allium cepa to study the cytological end-points, such as chromosome breaks and exchanges, which follow the testing of chemicals in somatic cells. It is considered that both mitotic and meiotic end-points should be used to a greater extent in assaying the cytogenetic effects of a chemical. From a literature survey, 148 chemicals are tabulated that have been assayed in 164 Allium tests for their clastogenic effect. Of the 164 assays which have been carried out, 75 are reported as giving a positive reaction, 49 positive and with a dose response, 1 positive and temperature-related, 9 borderline positive, and 30 negative; 76% of the chemicals gave a definite positive response. It is proposed that the Allium test be included among those tests routinely used for assessing chromosomal damage induced by chemicals.
A New Orthodontic Appliance with a Mini Screw for Upper Molar Distalization.
Ozkalayci, Nurhat; Yetmez, Mehmet
The aim of this study is to present a new upper molar distalization appliance called Cise distalizer designed as intraoral device supported with orthodontic mini screw for upper permanent molar distalization. The new appliance consists of eight main components. In order to understand the optimum force level, the appliance under static loading is tested by using strain gage measurement techniques. Results show that one of the open coils produces approximately 300 gr distalization force. Cise distalizer can provide totally 600 gr distalization force. This range of force level is enough for distalization of upper first and second molar teeth.
A New Orthodontic Appliance with a Mini Screw for Upper Molar Distalization
Directory of Open Access Journals (Sweden)
Nurhat Ozkalayci
Full Text Available The aim of this study is to present a new upper molar distalization appliance called Cise distalizer designed as intraoral device supported with orthodontic mini screw for upper permanent molar distalization. The new appliance consists of eight main components. In order to understand the optimum force level, the appliance under static loading is tested by using strain gage measurement techniques. Results show that one of the open coils produces approximately 300 gr distalization force. Cise distalizer can provide totally 600 gr distalization force. This range of force level is enough for distalization of upper first and second molar teeth.
Inter-chromosomal heterogeneity in the formation of radiation induced chromosomal aberrations
International Nuclear Information System (INIS)
Natarajan, A.T.; Vermeulen, S.; Boei, J.J.W.A.
It is generally assumed that radiation induced chromosomal lesions are distributed randomly and repaired randomly among the genome. Recent studies using fluorescent in situ hybridization (FISH) and chromosome specific DNA libraries indicate that some chromosomes are more sensitive for radiation induced aberration formation than others. Chromosome No. 4 in human and chromosome No. 8 in Chinese hamster have been found to involve more in exchange aberrations than others, when calculated on the basis of their DNA content. Painting with arm specific chromosome libraries indicate that the frequencies of radiation induced intra-chromosome exchanges (i.e., between the arms of a chromosome, such as centric rings and inversions) are far in excess than one would expect on the basis of the frequencies of observed inter-chromosomal exchanges. The possible factors leading to the observed heterogeneity will be discussed
Limited distal organelles and synaptic function in extensive monoaminergic innervation.
Tao, Juan; Bulgari, Dinara; Deitcher, David L; Levitan, Edwin S
Organelles such as neuropeptide-containing dense-core vesicles (DCVs) and mitochondria travel down axons to supply synaptic boutons. DCV distribution among en passant boutons in small axonal arbors is mediated by circulation with bidirectional capture. However, it is not known how organelles are distributed in extensive arbors associated with mammalian dopamine neuron vulnerability, and with volume transmission and neuromodulation by monoamines and neuropeptides. Therefore, we studied presynaptic organelle distribution in Drosophila octopamine neurons that innervate ∼20 muscles with ∼1500 boutons. Unlike in smaller arbors, distal boutons in these arbors contain fewer DCVs and mitochondria, although active zones are present. Absence of vesicle circulation is evident by proximal nascent DCV delivery, limited impact of retrograde transport and older distal DCVs. Traffic studies show that DCV axonal transport and synaptic capture are not scaled for extensive innervation, thus limiting distal delivery. Activity-induced synaptic endocytosis and synaptic neuropeptide release are also reduced distally. We propose that limits in organelle transport and synaptic capture compromise distal synapse maintenance and function in extensive axonal arbors, thereby affecting development, plasticity and vulnerability to neurodegenerative disease. © 2017. Published by The Company of Biologists Ltd.
Fractures of the distal radius in children: A retrospective evaluation
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Selma Yazıcı
Full Text Available Objectives: This study designed to evaluate the resultsof treatment, closed reduction and percutaneous wires, ofthe distal radius fractures in children.Materials and methods: A retrospective analysis wascarried out in children aged between 5-15 years who presentedwith a displaced fracture of the distal radius to ourhospital. They were initially treated with closed reductionand cast immobilization. If the fractures redisplaced treatedby percutaneous Kirschner (K- wire with scope undera general anaesthesia.Results: Totally 104 patients, who have distal radius fractureswere treated by closed reduction and immobilizationin a plaster cast. 13 patient who have distal radiusfractures were treated by closed reduction under generalanaesthesia and fixed by percutaneous Kirschner (K-wire. Patients with impaired the alignment of the fracturein late period were usually completely displaced fractures.(n=5, 4,3%, in early period, completely displaced fractures(n=5, 4,3% are superior to partial displaced fractures(n=2, 1,7%.Conclusion: In our study, when children with distal radiusfracture first come, they were treated by closed reductionand immobilization in a plaster cast. We thought that inredisplaced fractures patients were suitable for the closedreduction with percutaneous wire treatment.
Chromosomal divergence and evolutionary inferences in Rhodniini based on the chromosomal location of ribosomal genes
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Sebastian Pita
Full Text Available In this study, we used fluorescence in situ hybridisation to determine the chromosomal location of 45S rDNA clusters in 10 species of the tribe Rhodniini (Hemiptera: Reduviidae: Triatominae. The results showed striking inter and intraspecific variability, with the location of the rDNA clusters restricted to sex chromosomes with two patterns: either on one (X chromosome or both sex chromosomes (X and Y chromosomes. This variation occurs within a genus that has an unchanging diploid chromosome number (2n = 22, including 20 autosomes and 2 sex chromosomes and a similar chromosome size and genomic DNA content, reflecting a genome dynamic not revealed by these chromosome traits. The rDNA variation in closely related species and the intraspecific polymorphism in Rhodnius ecuadoriensis suggested that the chromosomal position of rDNA clusters might be a useful marker to identify recently diverged species or populations. We discuss the ancestral position of ribosomal genes in the tribe Rhodniini and the possible mechanisms involved in the variation of the rDNA clusters, including the loss of rDNA loci on the Y chromosome, transposition and ectopic pairing. The last two processes involve chromosomal exchanges between both sex chromosomes, in contrast to the widely accepted idea that the achiasmatic sex chromosomes of Heteroptera do not interchange sequences.
A novel partial deletion of the Y chromosome azoospermia factor c region is caused by non-homologous recombination between palindromes and may be associated with increased sperm counts
Noordam, M. J.; van Daalen, S. K. M.; Hovingh, S. E.; Korver, C. M.; van der Veen, F.; Repping, S.
BACKGROUND: The male-specific region of the human Y chromosome (MSY) contains multiple testis-specific genes. Most deletions in the MSY lead to inadequate or absent sperm production. Nearly all deletions occur via homologous recombination between amplicons. Previously, we identified two P5/distal-P1
The Mouse House: A brief history of the ORNL mouse-genetics program, 1947–2009
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Russell, Liane B.
The large mouse genetics program at the Oak Ridge National Lab is often re-membered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-Chromosome s importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a valuable
The Mouse House: a brief history of the ORNL mouse-genetics program, 1947-2009.
Russell, Liane B
The large mouse genetics program at the Oak Ridge National Laboratory (ORNL) is often remembered chiefly for the germ-cell mutation-rate data it generated and their uses in estimating the risk of heritable radiation damage. In fact, it soon became a multi-faceted research effort that, over a period of almost 60 years, generated a wealth of information in the areas of mammalian mutagenesis, basic genetics (later enriched by molecular techniques), cytogenetics, reproductive biology, biochemistry of germ cells, and teratology. Research in the area of germ-cell mutagenesis explored the important physical and biological factors that affect the frequency and nature of induced mutations and made several unexpected discoveries, such as the major importance of the perigametic interval (the zygote stage) for the origin of spontaneous mutations and for the sensitivity to induced genetic change. Of practical value was the discovery that ethylnitrosourea was a supermutagen for point mutations, making high-efficiency mutagenesis in the mouse feasible worldwide. Teratogenesis findings resulted in recommendations still generally accepted in radiological practice. Studies supporting the mutagenesis research added whole bodies of information about mammalian germ-cell development and about molecular targets in germ cells. The early decision to not merely count but propagate genetic variants of all sorts made possible further discoveries, such as the Y-chromosome's importance in mammalian sex determination and the identification of rare X-autosome translocations, which, in turn, led to the formulation of the single-active-X hypothesis and provided tools for studies of functional mosaicism for autosomal genes, male sterility, and chromosome-pairing mechanism. Extensive genetic and then molecular analyses of large numbers of induced specific-locus mutants resulted in fine-structure physical and correlated functional mapping of significant portions of the mouse genome and constituted a
Theory on the mechanism of distal action of transcription factors: looping of DNA versus tracking along DNA
International Nuclear Information System (INIS)
Murugan, R
In this paper, we develop a theory on the mechanism of distal action of the transcription factors, which are bound at their respective cis-regulatory enhancer modules on the promoter-RNA polymerase II (PR) complexes to initiate the transcription event in eukaryotes. We consider both the looping and tracking modes of their distal communication and calculate the mean first passage time that is required for the distal interactions of the complex of enhancer and transcription factor with the PR via both these modes. We further investigate how this mean first passage time is dependent on the length of the DNA segment (L, base-pairs) that connects the cis-regulatory binding site and the respective promoter. When the radius of curvature of this connecting segment of DNA is R that was induced upon binding of the transcription factor at the cis-acting element and RNAPII at the promoter in cis-positions, our calculations indicate that the looping mode of distal action will dominate when L is such that L > 2πR and the tracking mode of distal action will be favored when L 2 bps. It seems that the free energy associated with the binding of the transcription factor with its cis-acting element and the distance of this cis-acting element from the corresponding promoter of the gene of interest is negatively correlated. Our results suggest that the looping and tracking modes of distal action are concurrently operating on the transcription activation and the physics that determines the timescales associated with the looping/tracking in the mechanism of action of these transcription factors on the initiation of the transcription event must put a selection pressure on the distribution of the distances of cis-regulatory modules from their respective promoters of the genes. The computational analysis of the upstream sequences of promoters of various genes in the human and mouse genomes for the presence of putative cis-regulatory elements for a set of known transcription factors using
Laparoscopic versus open distal pancreatectomy for pancreatic cancer.
Riviere, Deniece; Gurusamy, Kurinchi Selvan; Kooby, David A; Vollmer, Charles M; Besselink, Marc G H; Davidson, Brian R; van Laarhoven, Cornelis J H M
Surgical resection is currently the only treatment with the potential for long-term survival and cure of pancreatic cancer. Surgical resection is provided as distal pancreatectomy for cancers of the body and tail of the pancreas. It can be performed by laparoscopic or open surgery. In operations on other organs, laparoscopic surgery has been shown to reduce complications and length of hospital stay as compared with open surgery. However, concerns remain about the safety of laparoscopic distal pancreatectomy compared with open distal pancreatectomy in terms of postoperative complications and oncological clearance. To assess the benefits and harms of laparoscopic distal pancreatectomy versus open distal pancreatectomy for people undergoing distal pancreatectomy for pancreatic ductal adenocarcinoma of the body or tail of the pancreas, or both. We used search strategies to search the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index Expanded and trials registers until June 2015 to identify randomised controlled trials (RCTs) and non-randomised studies. We also searched the reference lists of included trials to identify additional studies. We considered for inclusion in the review RCTs and non-randomised studies comparing laparoscopic versus open distal pancreatectomy in patients with resectable pancreatic cancer, irrespective of language, blinding or publication status.. Two review authors independently identified trials and independently extracted data. We calculated odds ratios (ORs), mean differences (MDs) or hazard ratios (HRs) along with 95% confidence intervals (CIs) using both fixed-effect and random-effects models with RevMan 5 on the basis of intention-to-treat analysis when possible. We found no RCTs on this topic. We included in this review 12 non-randomised studies that compared laparoscopic versus open distal pancreatectomy (1576 participants: 394 underwent laparoscopic distal pancreatectomy and 1182
Chromosome analysis of arsenic affected cattle
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S. Shekhar
Full Text Available Aim: The aim was to study the chromosome analysis of arsenic affected cattle. Materials and Methods: 27 female cattle (21 arsenic affected and 6 normal were selected for cytogenetical study. The blood samples were collected, incubated, and cultured using appropriate media and specific methods. The samples were analyzed for chromosome number and morphology, relative length of the chromosome, arm ratio, and centromere index of X chromosome and chromosomal abnormalities in arsenic affected cattle to that of normal ones. Results: The diploid number of metaphase chromosomes in arsenic affected cattle as well as in normal cattle were all 2n=60, 58 being autosomes and 2 being sex chromosomes. From the centromeric position, karyotyping studies revealed that all the 29 pair of autosomes was found to be acrocentric or telocentric, and the sex chromosomes (XX were submetacentric in both normal and arsenic affected cattle. The relative length of all the autosome pairs and sex chrosomosome pair was found to be higher in normal than that of arsenic affected cattle. The mean arm ratio of X-chromosome was higher in normal than that of arsenic affected cattle, but it is reverse in case of centromere index value of X-chromosome. There was no significant difference of arm ratio and centromere index of X-chromosomes between arsenic affected and normal cattle. No chromosomal abnormalities were found in arsenic affected cattle. Conclusion: The chromosome analysis of arsenic affected cattle in West Bengal reported for the first time in this present study which may serve as a guideline for future studies in other species. These reference values will also help in comparison of cytological studies of arsenic affected cattle to that of various toxicants.
Giant Cell Tumour of the Distal Ulna: A Rare Presentation
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Ruben Jaya Kumar
Full Text Available Giant-cell tumour (GCT of bone, a primary yet locally aggressive benign tumour, commonly affects patients between the ages of 20 and 40 years, with the peak incidence occurring in the third decade. Women are affected slightly more than men. The distal end of the ulna is an extremely uncommon site for primary bone tumours in general and giant cell tumours in particular. Wide resection of the distal ulna is the recommended treatment for GCT in such locations. Radio-ulna convergence and dorsal displacement of the ulna stump are known complications following ulna resection proximal to the insertion of the pronator quadratus. This leads to reduction in grip power and forearm rotatory motion. Stabilization of the ulna stump with extensor carpi ulnaris (ECU tendon after wide resection of the tumour has been described in the literature. We report a case of GCT of distal end of ulna treated with wide resection and stabilization with ECU tendon.
Segmental reversal of distal small intestine in short bowel syndrome
DEFF Research Database (Denmark)
Grave, Pernille Kock; Thomsen, Sabrina Valentin; Clark, Pia Susanne
were the influence on cell proliferation and mucosal architecture shown by histological analysis. Methods: Sixteen piglets underwent a 60% resection of the distal small intestine and were randomized into two groups. Group 1 short bowel syndrome alone (SBS) (n = 8) and group 2 with reversal of a distal...... small intestinal segment (SBS-RS) (n = 8). Body weight was measured daily and the pigs were euthanized after 1 month. Crypt depths, villus heights and muscle layers thicknesses were measured. For the evaluation of microvilli of the brush border of the epithelium and cell proliferation...... was found in the SBS group and increase in the thickness of the circular and longitudinal muscle layers in the SBS-RS group. In the distal ileal segment the longitudinal muscle layer thicknesses were increased in the SBS group. Otherwise, no significant changes were found. Conclusion: Reversal of a 20-cm...
Fractures of the distal tibia treated with polyaxial locking plating.
Gao, Hong; Zhang, Chang-Qing; Luo, Cong-Feng; Zhou, Zu-Bin; Zeng, Bing-Fang
We evaluated the healing rate, complications, and functional outcomes in 32 adult patients with very short metaphyseal fragments in fractures of the distal tibia treated with a polyaxial locking system. The average distance from the distal extent of the fracture to the tibial plafond was 11 mm. All fractures healed and the average time to union was 14 weeks. Six patients (19%) reported occasional local disturbance over the medial malleolus. There were two cases of postoperative superficial infections and evidence of delayed wound healing. Using the American Orthopaedic Foot and Ankle Society ankle score, the average functional score was 87.3 points (of 100 total possible points). Our results show the polyaxial locking plates, which offer more fixation versatility, may be a reasonable treatment option for distal tibia fractures with very short metaphyseal segments.
Minimally Invasive Distal Pancreatectomy: Review of the English Literature.
Wang, Kai; Fan, Ying
Recently, the superiority of the minimally invasive approach, which results in a better cosmetic result, faster recovery, and shorter length of hospital stay, is a technique that has been progressively recognized as it has developed. And the minimally invasive approach has been applied to distal pancreatectomy (DP), which is a standard method for the treatment of benign, borderline, and part of malignant lesions of the pancreatic body and tail. This article aims to analyze the types, postoperative recovery, and outcomes of laparoscopic distal pancreatectomy (LDP). A systematic search of the scientific literature was performed using PubMed, EMBASE, online journals, and the Internet for all publications on LDP. Articles were selected if the abstract contained patients who underwent LDP for pancreatic diseases. All selected articles were reviewed and analyzed. If there were no contraindications for LDP, this operation is suitable for benign, borderline, or malignant tumors of the pancreatic body and tail, which should try to be performed with preservation of the spleen. LDP is safe and feasible under some conditions to experienced surgeon. Single-incision laparoscopic distal pancreatectomy (S-LDP) and robotic laparoscopic distal pancreatectomy (R-LDP) perioperative outcomes are similar with conventional multi-incision laparoscopic distal pancreatectomy (C-LDP). And the advantages of S-LDP and R-LDP require further exploration. With the application of enhanced recovery program (ERP), length of hospital stay and costs are reduced. LDP is safe and feasible under some conditions. Compared with open distal pancreatectomy, LDP has a lot of advantages; a trend was observed for LDP to replace traditional open surgery. LDP combined with ERP is expected to become standard in the treatment of pancreatic body and tail lesions.
Laparoscopic distal pancreatectomy for adenocarcinoma: safe and reasonable?
Postlewait, Lauren M.
As a result of technological advances during the past two decades, surgeons now use minimally invasive surgery (MIS) approaches to pancreatic resection more frequently, yet the role of these approaches for pancreatic ductal adenocarcinoma resections remains uncertain, given the aggressive nature of this malignancy. Although there are no controlled trials comparing MIS technique to open surgical technique, laparoscopic distal pancreatectomy for pancreatic adenocarcinoma is performed with increasing frequency. Data from retrospective studies suggest that perioperative complication profiles between open and laparoscopic distal pancreatectomy are similar, with perhaps lower blood loss and fewer wound infections in the MIS group. Concerning oncologic outcomes, there appear to be no differences in the rate of achieving negative margins or in the number of lymph nodes (LNs) resected when compared to open surgery. There are limited recurrence and survival data on laparoscopic compared to open distal pancreatectomy for pancreatic adenocarcinoma, but in the few studies that assess long term outcomes, recurrence rates and survival outcomes appear similar. Recent studies show that though laparoscopic distal pancreatectomy entails a greater operative cost, the associated shorter length of hospital stay leads to decreased overall cost compared to open procedures. Multiple new technologies are emerging to improve resection of pancreatic cancer. Robotic pancreatectomy is feasible, but there are limited data on robotic resection of pancreatic adenocarcinoma, and outcomes appear similar to laparoscopic approaches. Additionally fluorescence-guided surgery represents a new technology on the horizon that could improve oncologic outcomes after resection of pancreatic adenocarcinoma, though published data thus far are limited to animal models. Overall, MIS distal pancreatectomy appears to be a safe and reasonable approach to treating selected patients with pancreatic ductal
Sequential actin-based pushing forces drive meiosis I chromosome migration and symmetry breaking in oocytes
Yi, Kexi; Rubinstein, Boris; Unruh, Jay R.; Guo, Fengli; Slaughter, Brian D.
Polar body extrusion during oocyte maturation is critically dependent on asymmetric positioning of the meiotic spindle, which is established through migration of the meiosis I (MI) spindle/chromosomes from the oocyte interior to a subcortical location. In this study, we show that MI chromosome migration is biphasic and driven by consecutive actin-based pushing forces regulated by two actin nucleators, Fmn2, a formin family protein, and the Arp2/3 complex. Fmn2 was recruited to endoplasmic reticulum structures surrounding the MI spindle, where it nucleated actin filaments to initiate an initially slow and poorly directed motion of the spindle away from the cell center. A fast and highly directed second migration phase was driven by actin-mediated cytoplasmic streaming and occurred as the chromosomes reach a sufficient proximity to the cortex to activate the Arp2/3 complex. We propose that decisive symmetry breaking in mouse oocytes results from Fmn2-mediated perturbation of spindle position and the positive feedback loop between chromosome signal-induced Arp2/3 activation and Arp2/3-orchestrated cytoplasmic streaming that transports the chromosomes. PMID:23439682
Chromosomal abnormalities in human glioblastomas: gain in chromosome 7p correlating with loss in chromosome 10q.
Inda, María del Mar; Fan, Xing; Muñoz, Jorge; Perot, Christine; Fauvet, Didier; Danglot, Giselle; Palacio, Ana; Madero, Pilar; Zazpe, Idoya; Portillo, Eduardo; Tuñón, Teresa; Martínez-Peñuela, José María; Alfaro, Jorge; Eiras, José; Bernheim, Alain; Castresana, Javier S
Various genomic alterations have been detected in glioblastoma. Chromosome 7p, with the epidermal growth factor receptor locus, together with chromosome 10q, with the phosphatase and tensin homologue deleted in chromosome 10 and deleted in malignant brain tumors-1 loci, and chromosome 9p, with the cyclin-dependent kinase inhibitor 2A locus, are among the most frequently damaged chromosomal regions in glioblastoma. In this study, we evaluated the genetic status of 32 glioblastomas by comparative genomic hybridization; the sensitivity of comparative genomic hybridization versus differential polymerase chain reaction to detect deletions at the phosphatase and tensin homologue deleted in chromosome 10, deleted in malignant brain tumors-1, and cyclin-dependent kinase inhibitor 2A loci and amplifications at the cyclin-dependent kinase 4 locus; the frequency of genetic lesions (gain or loss) at 16 different selected loci (including oncogenes, tumor-suppressor genes, and proliferation markers) mapping on 13 different chromosomes; and the possible existence of a statistical association between any pair of molecular markers studied, to subdivide the glioblastoma entity molecularly. Comparative genomic hybridization showed that the most frequent region of gain was chromosome 7p, whereas the most frequent losses occurred on chromosomes 10q and 13q. The only statistically significant association was found for 7p gain and 10q loss. Copyright 2002 Wiley-Liss, Inc.
Persistence of chromosomal abnormalities additional to the Philadelphia chromosome after Philadelphia chromosome disappearance during imatinib therapy for chronic myeloid leukemia.
Zaccaria, Alfonso; Valenti, Anna Maria; Donti, Emilio; Gozzetti, Alessandro; Ronconi, Sonia; Spedicato, Francesco
Five Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) patients with additional chromosome abnormalities at diagnosis have been followed during Imatinib therapy. In all, the Ph chromosome disappeared, while the 5 cases, additional abnormalities [dup(1); del(5), +8 (2 patients) and +14] persisted in the subsequent studies, performed over a period of 11 to 49 months, either alone or together with a karyotypically normal cell population. This finding is consistent with a secondary origin of the Ph chromosome in these patients. It is still to early to evaluate the possible prognostic value of these additional abnormalities.
Chromosomal evolution of the PKD1 gene family in primates
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Krawczak Michael
Full Text Available Abstract Background The autosomal dominant polycystic kidney disease (ADPKD is mostly caused by mutations in the PKD1 (polycystic kidney disease 1 gene located in 16p13.3. Moreover, there are six pseudogenes of PKD1 that are located proximal to the master gene in 16p13.1. In contrast, no pseudogene could be detected in the mouse genome, only a single copy gene on chromosome 17. The question arises how the human situation originated phylogenetically. To address this question we applied comparative FISH-mapping of a human PKD1-containing genomic BAC clone and a PKD1-cDNA clone to chromosomes of a variety of primate species and the dog as a non-primate outgroup species. Results Comparative FISH with the PKD1-cDNA clone clearly shows that in all primate species studied distinct single signals map in subtelomeric chromosomal positions orthologous to the short arm of human chromosome 16 harbouring the master PKD1 gene. Only in human and African great apes, but not in orangutan, FISH with both BAC and cDNA clones reveals additional signal clusters located proximal of and clearly separated from the PKD1 master genes indicating the chromosomal position of PKD1 pseudogenes in 16p of these species, respectively. Indeed, this is in accordance with sequencing data in human, chimpanzee and orangutan. Apart from the master PKD1 gene, six pseudogenes are identified in both, human and chimpanzee, while only a single-copy gene is present in the whole-genome sequence of orangutan. The phylogenetic reconstruction of the PKD1-tree reveals that all human pseudogenes are closely related to the human PKD1 gene, and all chimpanzee pseudogenes are closely related to the chimpanzee PKD1 gene. However, our statistical analyses provide strong indication that gene conversion events may have occurred within the PKD1 family members of human and chimpanzee, respectively. Conclusion PKD1 must have undergone amplification very recently in hominid evolution. Duplicative
Neglected Distal Humeral Epiphyseal Injury - Two Case Reports
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Dr. Pankaj Kumar
Full Text Available Distal humeral epiphyseal separation is an uncommon injury in children, which can be missed or misdiagnosed at initial presentation. Awareness of this injury and appropriate radiological assessment helps in proper management. Neglected cases because of inappropriate diagnosis can result in cubitus varus deformity. Full range of movements of elbow can be achieved if properly diagnosed and managed. We present two cases of neglected distal humeral epiphyseal injury in children that resulted in cubitus varus deformity in one case. Full range of movements was achieved in both cases after proper management.
Distal vertebral artery reconstruction when managing vertebrobasilar insufficiency
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D. M. Galaktionov
Full Text Available This article presents a literature review devoted to the reconstruction of the distal vertebral artery and a clinical case of successful surgical treatment of a patient suffering from vertebrobasilar insufficiency caused by occlusion of the vertebral artery in a proximal segment. The external carotid artery-distal vertebral artery bypass was performed by using the radial artery.Received 27 February 2017. Revised 25 July 2017. Accepted 3 August 2017.Funding: The study did not have sponsorship.Conflict of interest: The authors declare no conflict of interest.
Robotic spleen-preserving distal pancreatectomy. A case report.
Vasilescu, C; Sgarbura, O; Tudor, S; Herlea, V; Popescu, I
Distal pancreatectomy (DP) is the removal of the pancreatic tissue at the left side of the superior mesenteric vein and it is traditionally approached by an open or laparoscopic exposure. Preservation of the spleen is optional but appears to have a better immunological outcome. We present the case of a 53-year old patient with a 2.4/2.2 tumor located in the tail of the pancreas, with high tumour marker values for whom we decided to perform a robotic spleen-preserving distal pancreatectomy (RSPDP). The postoperative outcome was satisfactory. In conclusion, we recommend this type of approach for small pancreatic tail lesions.
Locking plates in distal humerus fractures: study of 43 patients
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Gupta Rakesh Kumar
Full Text Available 【Abstract】Objective: The treatment of multi-fragmentary, intraarticular fractures of the distal humerus is difficult, even in young patients with bone of good quality. Small distal fragment, diminished bone mineral quality and increased trauma-associated joint destruction make stable joint reconstruction more problematic. The anatomically preshaped locking plates allow angular stable fixation for these complex fractures. We evaluated functional results of patients treated with open reduction and internal fixation with distal humerus locking plates for complex distal hu-merus fractures. Methods: Forty-three consecutive patients with ar-ticular fractures of the distal humerus were treated by open reduction and internal fixation with AO distal humerus plate system and locking reconstruction plates. Forty patients were available for the final outcome analysis. According to AO/ASIF classification, there were 2 cases of type A2, 4 cases of type A3, 1 case of type B1, 1 case of type B2, 14 cases of type C1, 7 cases of type C2 and 11 cases of type C3. Open reduction with triceps splitting technique was used in all patients. The clinical and radiographic follow-up was performed and outcome measures included pain assessment, range of motion, and Mayo elbow performance score. Results: Forty patients were available for the final outcome analysis. There were 29 males and 11 females with an average age of 38.4 years (18-73 years. Clinical and ra-diological consolidation of the fracture was observed in all cases at an average of 11.6 weeks (9-14 weeks. The average follow-up was 12 months (10-18 months. Using the Mayo elbow performance score the results obtained were graded as excellent or good results in 33 patients (82.5%. One pa-tient had superficial infection, and 4 had myositis ossificans. There were no cases of primary malposition or secondary displacement, implant failure or ulnar neuropathy. Conclusion: Anatomically preshaped distal humerus locking
Traumatisk distal humerus-epifysiolyse hos nyfødt
DEFF Research Database (Denmark)
Al-Aubaidi, Zaid; Nielsen, Keld Daubjerg
Traumatic distal humerus epiphysiolysis (TDHE) is a rare injury in infants with an incidence of about 1:35,000 births. It is primarily a birth injury, but it is also seen in cases of battered child syndrome. Because of its rare occurrence and the diagnostic difficulties, the lesion may be overloo......Traumatic distal humerus epiphysiolysis (TDHE) is a rare injury in infants with an incidence of about 1:35,000 births. It is primarily a birth injury, but it is also seen in cases of battered child syndrome. Because of its rare occurrence and the diagnostic difficulties, the lesion may...
Primary bone lymphoma of the distal tibia mimicking brodie's abscess
International Nuclear Information System (INIS)
Park, Jina; Lee, Seung Hun; Joo, Kyung Bin; Park, Chan Kum
The 'penumbra sign' on an unenhanced T1-weighted image is a well-known characteristic of Brodie's abscess, and this sign is extremely helpful for discriminating subacute osteomyelitis from other bone lesions. We present a case of primary bone lymphoma of the distal tibia mimicking subacute osteomyelitis with Brodie's abscess in a 50-year-old woman. Initial radiographs and MRI showed a lesion in the distal tibia consistent with Brodie's abscess with the penumbra sign. Histopathological examination of the surgical biopsy specimen confirmed the presence of a diffuse large B-cell lymphoma involving the bone.
Nontraumatic osteonecrosis of the distal pole of the scaphoid
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Bhavuk Garg
Full Text Available Post traumatic osteonecrosis of distal pole of scaphoid is very rare. We present a case of 34 years old male, drill operator by occupation with nontraumatic osteonecrosis of distal pole of the scaphoid. The patient was managed conservatively and was kept under regular follow-up every three months. The patient was also asked to change his profession. Two years later, the patient had no pain and had mild restriction of wrist movements (less than 15 degrees in either direction. The radiographs revealed normal density of the scaphoid suggesting revascularization.
Osteoblastoma-like osteosarcoma of the distal tibia
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Abramovici, Luigia; Steiner, German C. [Department of Pathology and Laboratory Medicine, Hospital for Joint Diseases, New York, NY (United States); Kenan, Samuel [Department of Orthopaedic Oncology Surgery, Hospital for Joint Diseases, New York, NY (United States); Hytiroglou, Prodromos [Aristotle University, Thessaloniki (Greece); Rafii, Mahvash [Department of Radiology, Hospital for Joint Diseases, New York, NY (United States)
We report a case of a 14-year-old boy with an intracompartmental lytic lesion with poorly defined margins in the right distal tibia that was originally treated with curettage and bone grafting. Histologic examination showed an osteoblastic tumor with unusual features, which was found on consultation to be an osteoblastoma-like osteosarcoma, a rare, low-grade variant of osteosarcoma. Subsequently, the patient underwent en bloc resection of the distal tibia, which was replaced with vascularized bone graft and followed by chemotherapy. Two years later, he is alive with lung metastases. (orig.)
Osteoblastoma-like osteosarcoma of the distal tibia
International Nuclear Information System (INIS)
Abramovici, Luigia; Steiner, German C.; Kenan, Samuel; Hytiroglou, Prodromos; Rafii, Mahvash
We report a case of a 14-year-old boy with an intracompartmental lytic lesion with poorly defined margins in the right distal tibia that was originally treated with curettage and bone grafting. Histologic examination showed an osteoblastic tumor with unusual features, which was found on consultation to be an osteoblastoma-like osteosarcoma, a rare, low-grade variant of osteosarcoma. Subsequently, the patient underwent en bloc resection of the distal tibia, which was replaced with vascularized bone graft and followed by chemotherapy. Two years later, he is alive with lung metastases. (orig.)
Distal renal tubular acidosis and amelogenesis imperfecta: A rare association
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P Ravi
Full Text Available Renal tubular acidosis (RTA is characterized by a normal anion gap with hyperchloremic metabolic acidosis. Primary distal RTA (type I is the most common RTA in children. Childhood presentation of distal RTA includes vomiting, failure to thrive, metabolic acidosis, and hypokalemia. Amelogenesis imperfecta (AI represents a condition where the dental enamel and oral tissues are affected in an equal manner resulting in the hypoplastic or hypopigmented teeth. We report a 10-year-old girl, previously asymptomatic presented with the hypokalemic paralysis and on work-up found out to have type I RTA. The discoloration of teeth and enamel was diagnosed as AI.
Modified distal shoe appliance--fabrication and clinical performance.
Gujjar, Kumar Raghav; Indushekar, K R; Amith, H V; Sharma, Shefali Li
When the primary second molar is prematurely lost, mesial movement and migration of the permanent first molar often occurs. This is one of the most difficult problems of the developing dentition confronted by pediatric dentists. Use of a space maintainer that will guide the permanent first molar into its normal position is indicated. In cases with bilateral premature loss of primary molars, the conventional design of distal shoe poses a variety of problems and, therefore, necessitates a customized design for the eruption guidance of permanent first molars. The purpose of this case report is to discuss an innovative design of a distal shoe appliance, which was used with good clinical results.
Screening renal stone formers for distal renal tubular acidosis
DEFF Research Database (Denmark)
Osther, P J; Hansen, A B; Røhl, H F
A group of 110 consecutive renal stone formers were screened for distal renal tubular acidosis (RTA) using morning fasting urinary pH (mfUpH) levels followed by a short ammonium chloride loading test in patients with levels above 6.0. In 14 patients (12.7%) a renal acidification defect was noted...... RTA in renal stone formers. Regardless of whether the acidification defect is primary or secondary to stone formation, however, all renal stone formers with distal RTA can expect to benefit from prophylactic alkaline therapy and it is recommended that the screening procedure, which is easy to use...
The probability to initiate X chromosome inactivation is determined by the X to autosomal ratio and X chromosome specific allelic properties.
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Kim Monkhorst
Full Text Available In female mammalian cells, random X chromosome inactivation (XCI equalizes the dosage of X-encoded gene products to that in male cells. XCI is a stochastic process, in which each X chromosome has a probability to be inactivated. To obtain more insight in the factors setting up this probability, we studied the role of the X to autosome (X ratio A ratio in initiation of XCI, and have used the experimental data in a computer simulation model to study the cellular population dynamics of XCI.To obtain more insight in the role of the XratioA ratio in initiation of XCI, we generated triploid mouse ES cells by fusion of haploid round spermatids with diploid female and male ES cells. These fusion experiments resulted in only XXY triploid ES cells. XYY and XXX ES lines were absent, suggesting cell death related either to insufficient X-chromosomal gene dosage (XYY or to inheritance of an epigenetically modified X chromosome (XXX. Analysis of active (Xa and inactive (Xi X chromosomes in the obtained triploid XXY lines indicated that the initiation frequency of XCI is low, resulting in a mixed population of XaXiY and XaXaY cells, in which the XaXiY cells have a small proliferative advantage. This result, and findings on XCI in diploid and tetraploid ES cell lines with different X ratio A ratios, provides evidence that the X ratio A ratio determines the probability for a given X chromosome to be inactivated. Furthermore, we found that the kinetics of the XCI process can be simulated using a probability for an X chromosome to be inactivated that is proportional to the X ratio A ratio. These simulation studies re-emphasize our hypothesis that the probability is a function of the concentration of an X-encoded activator of XCI, and of X chromosome specific allelic properties determining the threshold for this activator.The present findings reveal that the probability for an X chromosome to be inactivated is proportional to the X ratio A ratio. This finding
Cloning of the gene for ocular albinism type 1 from the distal short arm of the X chromosome
Bassi, M. T.; Schiaffino, M. V.; Renieri, A.; de Nigris, F.; Galli, L.; Bruttini, M.; Gebbia, M.; Bergen, A. A.; Lewis, R. A.; Ballabio, A.
Ocular albinism type 1 (OA1) is an X-linked disorder characterized by severe impairment of visual acuity, retinal hypopigmentation and the presence of macromelanosomes. We isolated a novel transcript from the OA1 critical region in Xp22.3-22.2 which is expressed at high levels in RNA samples from
Development and Characterization of a Human and Mouse Intestinal Epithelial Cell Monolayer Platform
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Kenji Kozuka
Full Text Available Summary: We describe the development and characterization of a mouse and human epithelial cell monolayer platform of the small and large intestines, with a broad range of potential applications including the discovery and development of minimally systemic drug candidates. Culture conditions for each intestinal segment were optimized by correlating monolayer global gene expression with the corresponding tissue segment. The monolayers polarized, formed tight junctions, and contained a diversity of intestinal epithelial cell lineages. Ion transport phenotypes of monolayers from the proximal and distal colon and small intestine matched the known and unique physiology of these intestinal segments. The cultures secreted serotonin, GLP-1, and FGF19 and upregulated the epithelial sodium channel in response to known biologically active agents, suggesting intact secretory and absorptive functions. A screen of over 2,000 pharmacologically active compounds for inhibition of potassium ion transport in the mouse distal colon cultures led to the identification of a tool compound. : Siegel and colleagues describe their development of a human and mouse intestinal epithelial cell monolayer platform that maintains the cellular, molecular, and functional characteristics of tissue for each intestinal segment. They demonstrate the platform's application to drug discovery by screening a library of over 2,000 compounds to identify an inhibitor of potassium ion transport in the mouse distal colon. Keywords: intestinal epithelium, organoids, monolayer, colon, small intestine, phenotype screening assays, enteroid, colonoid
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Chromosome engineering: power tools for plant genetics.
Chan, Simon W L
The term "chromosome engineering" describes technologies in which chromosomes are manipulated to change their mode of genetic inheritance. This review examines recent innovations in chromosome engineering that promise to greatly increase the efficiency of plant breeding. Haploid Arabidopsis thaliana have been produced by altering the kinetochore protein CENH3, yielding instant homozygous lines. Haploid production will facilitate reverse breeding, a method that downregulates recombination to ensure progeny contain intact parental chromosomes. Another chromosome engineering success is the conversion of meiosis into mitosis, which produces diploid gametes that are clones of the parent plant. This is a key step in apomixis (asexual reproduction through seeds) and could help to preserve hybrid vigor in the future. New homologous recombination methods in plants will potentiate many chromosome engineering applications. Copyright © 2010 Elsevier Ltd. All rights reserved.
Higher 5-hydroxymethylcytosine identifies immortal DNA strand chromosomes in asymmetrically self-renewing distributed stem cells.
Huh, Yang Hoon; Cohen, Justin; Sherley, James L
Immortal strands are the targeted chromosomal DNA strands of nonrandom sister chromatid segregation, a mitotic chromosome segregation pattern unique to asymmetrically self-renewing distributed stem cells (DSCs). By nonrandom segregation, immortal DNA strands become the oldest DNA strands in asymmetrically self-renewing DSCs. Nonrandom segregation of immortal DNA strands may limit DSC mutagenesis, preserve DSC fate, and contribute to DSC aging. The mechanisms responsible for specification and maintenance of immortal DNA strands are unknown. To discover clues to these mechanisms, we investigated the 5-methylcytosine and 5-hydroxymethylcytosine (5hmC) content on chromosomes in mouse hair follicle DSCs during nonrandom segregation. Although 5-methylcytosine content did not differ significantly, the relative content of 5hmC was significantly higher in chromosomes containing immortal DNA strands than in opposed mitotic chromosomes containing younger mortal DNA strands. The difference in relative 5hmC content was caused by the loss of 5hmC from mortal chromosomes. These findings implicate higher 5hmC as a specific molecular determinant of immortal DNA strand chromosomes. Because 5hmC is an intermediate during DNA demethylation, we propose a ten-eleven translocase enzyme mechanism for both the specification and maintenance of nonrandomly segregated immortal DNA strands. The proposed mechanism reveals a means by which DSCs "know" the generational age of immortal DNA strands. The mechanism is supported by molecular expression data and accounts for the selection of newly replicated DNA strands when nonrandom segregation is initiated. These mechanistic insights also provide a possible basis for another characteristic property of immortal DNA strands, their guanine ribonucleotide dependency.
Genetic mapping of xenotropic murine leukemia virus-inducing loci in five mouse strains.
Kozak, C A; Rowe, W P
A single mendelian gene was identified for induction of the endogenous xenotropic murine leukemia virus in five mouse strains (C57BL/10, C57L, C57BR, AKR, and BALB/c). This locus, designated Bxv-1, mapped to the same site on chromosome 1 in all strains: Id-1-Pep-3-[Bxv-1-Lp]. Thus, inducibility loci for xenotropic virus are more limited in number and chromosomal distribution than ecotropic inducibility loci. Virus expression in mice with Bxv-1 was induced by treatment of fibroblasts with 5-iododeoxyuridine or by exposure of spleen cells to a B cell mitogen, bacterial lipopolysaccharide. An analysis of the hamster X mouse somatic cell hybrids indicated that chromosome 1, alone, was sufficient for virus induction.
Loss of Ubr2, an E3 ubiquitin ligase, leads to chromosome fragility and impaired homologous recombinational repair
International Nuclear Information System (INIS)
Ouyang, Yan; Kwon, Yong Tae; An, Jee Young; Eller, Danny; Tsai, S.-C.; Diaz-Perez, Silvia; Troke, Joshua J.; Teitell, Michael A.; Marahrens, York
The N-end rule pathway of protein degradation targets proteins with destabilizing N-terminal residues. Ubr2 is one of the E3 ubiquitin ligases of the mouse N-end rule pathway. We have previously shown that Ubr2 -/- male mice are infertile, owing to the arrest of spermatocytes between the leptotene/zygotene and pachytene of meiosis I, the failure of chromosome pairing, and subsequent apoptosis. Here, we report that mouse fibroblast cells derived from Ubr2 -/- embryos display genome instability. The frequency of chromosomal bridges and micronuclei were much higher in Ubr2 -/- fibroblasts than in +/+ controls. Metaphase chromosome spreads from Ubr2 -/- cells revealed a high incidence of spontaneous chromosomal gaps, indicating chromosomal fragility. These fragile sites were generally replicated late in S phase. Ubr2 -/- cells were hypersensitive to mitomycin C, a DNA cross-linking agent, but displayed normal sensitivity to gamma-irradiation. A reporter assay showed that Ubr2 -/- cells are significantly impaired in the homologous recombination repair of a double strand break. In contrast, Ubr2 -/- cells appeared normal in an assay for non-homologous end joining. Our results therefore unveil the role of the ubiquitin ligase Ubr2 in maintaining genome integrity and in homologous recombination repair
Loss of Ubr2, an E3 ubiquitin ligase, leads to chromosome fragility and impaired homologous recombinational repair
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Ouyang, Yan [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Kwon, Yong Tae [Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261 (United States); An, Jee Young [Center for Pharmacogenetics and Department of Pharmaceutical Sciences, University of Pittsburgh, Pittsburgh, PA 15261 (United States); Eller, Danny [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Tsai, S.-C. [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Diaz-Perez, Silvia [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Troke, Joshua J. [Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Teitell, Michael A. [Department of Pathology and Laboratory Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States); Marahrens, York [Department of Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095 (United States)]. E-mail: firstname.lastname@example.com
The N-end rule pathway of protein degradation targets proteins with destabilizing N-terminal residues. Ubr2 is one of the E3 ubiquitin ligases of the mouse N-end rule pathway. We have previously shown that Ubr2{sup -/-} male mice are infertile, owing to the arrest of spermatocytes between the leptotene/zygotene and pachytene of meiosis I, the failure of chromosome pairing, and subsequent apoptosis. Here, we report that mouse fibroblast cells derived from Ubr2{sup -/-} embryos display genome instability. The frequency of chromosomal bridges and micronuclei were much higher in Ubr2{sup -/-} fibroblasts than in +/+ controls. Metaphase chromosome spreads from Ubr2{sup -/-} cells revealed a high incidence of spontaneous chromosomal gaps, indicating chromosomal fragility. These fragile sites were generally replicated late in S phase. Ubr2{sup -/-} cells were hypersensitive to mitomycin C, a DNA cross-linking agent, but displayed normal sensitivity to gamma-irradiation. A reporter assay showed that Ubr2{sup -/-} cells are significantly impaired in the homologous recombination repair of a double strand break. In contrast, Ubr2{sup -/-} cells appeared normal in an assay for non-homologous end joining. Our results therefore unveil the role of the ubiquitin ligase Ubr2 in maintaining genome integrity and in homologous recombination repair.
Genetic recombination variation in wild Robertsonian mice: on the role of chromosomal fusions and Prdm9 allelic background.
Capilla, Laia; Medarde, Nuria; Alemany-Schmidt, Alexandra; Oliver-Bonet, Maria; Ventura, Jacint; Ruiz-Herrera, Aurora
Despite the existence of formal models to explain how chromosomal rearrangements can be fixed in a population in the presence of gene flow, few empirical data are available regarding the mechanisms by which genome shuffling contributes to speciation, especially in mammals. In order to shed light on this intriguing evolutionary process, here we present a detailed empirical study that shows how Robertsonian (Rb) fusions alter the chromosomal distribution of recombination events during the formation of the germline in a Rb system of the western house mouse (Mus musculus domesticus). Our results indicate that both the total number of meiotic crossovers and the chromosomal distribution of recombination events are reduced in mice with Rb fusions and that this can be related to alterations in epigenetic signatures for heterochromatinization. Furthermore, we detected novel house mouse Prdm9 allelic variants in the Rb system. Remarkably, mean recombination rates were positively correlated with a decrease in the number of ZnF domains in the Prdm9 gene. The suggestion that recombination can be modulated by both chromosomal reorganizations and genetic determinants that control the formation of double-stranded breaks during meiosis opens new avenues for understanding the role of recombination in chromosomal speciation. © 2014 The Author(s) Published by the Royal Society. All rights reserved.
Distally based superficial sural artery flap for soft tissue coverage in the distal 2/3 of leg and foot
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Kamath B
Full Text Available Background: Skin coverage for defects in the lower 2/3 of leg, ankle region and posterior heel has always been a difficult challenge for reconstructive surgeon. Methods: We describe our experience with the distally based superficial sural artery flap coverage in 48 patients with moderate sized defects in these difficult areas. Results: One out of 48 flaps (in 48 patients was lost totally and 3 suffered marginal necrosis which did not require any secondary procedure. These complications could have been avoided by proper selection of cases and refining technical skills. Conclusion: This simple procedure could be an important and versatile tool for any reconstructive surgeon in providing skin coverage in the distal leg and proximal foot. Preservation of major arteries of the lower limb, minimal donor defect, relatively uninjured donor area in compound fracture or poly trauma involving distal leg are some of the advantages of the flap.
Advances in plant chromosome genomics
Czech Academy of Sciences Publication Activity Database
Doležel, Jaroslav; Vrána, Jan; Cápal, Petr; Kubaláková, Marie; Burešová, Veronika; Šimková, Hana
Roč. 32, č. 1 (2014), s. 122-136 ISSN 0734-9750 R&D Projects: GA ČR GAP501/10/1740; GA ČR GAP501/10/1778; GA ČR GBP501/12/G090; GA MŠk(CZ) LO1204 Grant - others:GA MŠk(CZ) ED0007/01/01 Program:ED Institutional support: RVO:61389030 Keywords : BAC library * Chromosome sorting * Cytogenetics Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 9.015, year: 2014
DEFF Research Database (Denmark)
Mateo, Julio C.; San Agustin, Javier; Hansen, John Paulin
Facial EMG for selection is fast, easy and, combined with gaze pointing, it can provide completely hands-free interaction. In this pilot study, 5 participants performed a simple point-and-select task using mouse or gaze for pointing and a mouse button or a facial-EMG switch for selection. Gaze...
Giemsa C-banding of Barley Chromosomes. IV. Chromosomal Constitution of Autotetraploid Barley
DEFF Research Database (Denmark)
Linde-Laursen, Ib
The progeny of an autotetraploid barley plant (C1) consisted of 45 tetraploids and 33 aneuploids. Giemsa C-banding was used to identify each of the chromosomes in 20 euploid and 31 aneuploid C2--seedlings, and in 11 C3--offspring of aneuploid C2--plants. The euploid C2--seedlings all had four...... homologues of each of the chromosomes. The aneuploid C2--seedlings were fairly equally distributed on hypo-and hyperploids, and on the seven chromosome groups. This suggests that a particular chromosome is lost or gained at random in gametes and embryos. The 11 C3--seedlings comprised seven true euploids......, one seedling with 2n=28 having an extra chromosome 6 and missing one chromosome 3, and three seedlings with 2n=29. The chromosomal composition of aneuploid C3--seedlings did not reflect that of their aneuploid C2--parents with respect to missing or extra chromosomes. Two hypohexaploid C2--seedlings...
Identification of distal silencing elements in the murine interferon-A11 gene promoter.
Roffet, P; Lopez, S; Navarro, S; Bandu, M T; Coulombel, C; Vignal, M; Doly, J; Vodjdani, G
The murine interferon-A11 (Mu IFN-A11) gene is a member of the IFN-A multigenic family. In mouse L929 cells, the weak response of the gene's promoter to viral induction is due to a combination of both a point mutation in the virus responsive element (VRE) and the presence of negatively regulating sequences surrounding the VRE. In the distal part of the promoter, the negatively acting E1E2 sequence was delimited. This sequence displays an inhibitory effect in either orientation or position on the inducibility of a virus-responsive heterologous promoter. It selectively represses VRE-dependent transcription but is not able to reduce the transcriptional activity of a VRE-lacking promoter. In a transient transfection assay, an E1E2-containing DNA competitor was able to derepress the native Mu IFN-A11 promoter. Specific nuclear factors bind to this sequence; thus the binding of trans-regulators participates in the repression of the Mu IFN-A11 gene. The E1E2 sequence contains an IFN regulatory factor (IRF)-binding site. Recombinant IRF2 binds this sequence and anti-IRF2 antibodies supershift a major complex formed with nuclear extracts. The protein composing the complex is 50 kDa in size, indicating the presence of IRF2 or antigenically related proteins in the complex. The Mu IFN-A11 gene is the first example within the murine IFN-A family, in which a distal promoter element has been identified that can negatively modulate the transcriptional response to viral induction.
Identification of quiescent, stem-like cells in the distal female reproductive tract.
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Yongyi Wang
Full Text Available In fertile women, the endometrium undergoes regular cycles of tissue build-up and regression. It is likely that uterine stem cells are involved in this remarkable turn over. The main goal of our current investigations was to identify slow-cycling (quiescent endometrial stem cells by means of a pulse-chase approach to selectively earmark, prospectively isolate, and characterize label-retaining cells (LRCs. To this aim, transgenic mice expressing histone2B-GFP (H2B-GFP in a Tet-inducible fashion were administered doxycycline (pulse which was thereafter withdrawn from the drinking water (chase. Over time, dividing cells progressively loose GFP signal whereas infrequently dividing cells retain H2B-GFP expression. We evaluated H2B-GFP retaining cells at different chase time points and identified long-term (LT; >12 weeks LRCs. The LT-LRCs are negative for estrogen receptor-α and express low levels of progesterone receptors. LRCs sorted by FACS are able to form spheroids capable of self-renewal and differentiation. Upon serum stimulation spheroid cells are induced to differentiate and form glandular structures which express markers of mature műllerian epithelial cells. Overall, the results indicate that quiescent cells located in the distal oviduct have stem-like properties and can differentiate into distinct cell lineages specific of endometrium, proximal and distal oviduct. Future lineage-tracing studies will elucidate the role played by these cells in homeostasis, tissue injury and cancer of the female reproductive tract in the mouse and eventually in man.
Exceptional Complex Chromosomal Rearrangements in Three Generations
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Hannie Kartapradja
Full Text Available We report an exceptional complex chromosomal rearrangement (CCR found in three individuals in a family that involves 4 chromosomes with 5 breakpoints. The CCR was ascertained in a phenotypically abnormal newborn with additional chromosomal material on the short arm of chromosome 4. Maternal karyotyping indicated that the mother carried an apparently balanced CCR involving chromosomes 4, 6, 11, and 18. Maternal transmission of the derivative chromosome 4 resulted in partial trisomy for chromosomes 6q and 18q and a partial monosomy of chromosome 4p in the proband. Further family studies found that the maternal grandmother carried the same apparently balanced CCR as the proband's mother, which was confirmed using the whole chromosome painting (WCP FISH. High resolution whole genome microarray analysis of DNA from the proband's mother found no evidence for copy number imbalance in the vicinity of the CCR translocation breakpoints, or elsewhere in the genome, providing evidence that the mother's and grandmother's CCRs were balanced at a molecular level. This structural rearrangement can be categorized as an exceptional CCR due to its complexity and is a rare example of an exceptional CCR being transmitted in balanced and/or unbalanced form across three generations.
Evaluation of Chromosomal Abnormalities and Common ...
African Journals Online (AJOL)
Evaluation of Chromosomal Abnormalities and Common Trombophilic Mutations in Cases with Recurrent Miscarriage. Ahmet Karatas, Recep Eroz, Mustafa Albayrak, Tulay Ozlu, Bulent Cakmak, Fatih Keskin ...
Reflections and meditations upon complex chromosomal exchanges.
Savage, John R K
The application of FISH chromosome painting techniques, especially the recent mFISH (and its equivalents) where all 23 human chromosome pairs can be distinguished, has demonstrated that many chromosome-type structural exchanges are much more complicated (involving more "break-rejoins" and arms) than has hitherto been assumed. It is clear that we have been greatly under-estimating the damage produced in chromatin by such agents as ionising radiation. This article gives a brief historical summary of observations leading up to this conclusion, and after outlining some of the problems surrounding the formation of complex chromosomes exchanges, speculates about possible solutions currently being proposed.
Chromosomal aberrations in ore miners of Slovakia
International Nuclear Information System (INIS)
Beno, M.; Vladar, M.; Nikodemova, D.; Vicanova, M.; Durcik, M.
A pilot study was performed in which the incidence of chromosomal aberrations in lymphocytes of miners in ore mines located in Central Slovakia was monitored and related to lifetime underground radon exposure and to lifetime smoking. The conclusions drawn from the results of the study were as follows: the counts of chromosomal aberrations in lymphocytes of miners were significantly higher than in an age matched control group of white-collar staff; the higher counts of chromosomal aberrations could be ascribed to underground exposure of miners and to smoking; a dependence of chromosomal aberration counts on the exposure to radon could not be assessed. (A.K.)
Chromosome heteromorphisms in the Japanese, 3
International Nuclear Information System (INIS)
Sofuni, Toshio; Awa, A.A.
The type and frequency of chromosome variants detected by the C-staining method were ascertained in 1,857 individuals residing in Hiroshima. The most frequent heteromorphic variant was the total inversion of the C-band in chromosome 9 found in 27 individuals (1.45%). The total inversion of the C-band in chromosome 1 was not seen in this sample, but the partial inversion of the C-band in chromosome 1 was found in 18 persons (0.97%). Partial inversion was also detected in the C-band in chromosome 9 in 22 individuals (1.18%). In chromosome 16, neither total nor partial inversion of the C-band was observed in the present study. The frequencies of chromosomes 1, 9, and 16 with a very large C-band were 0.70%, 0.22%, and 0.54%, respectively. Aside from these (1, 9, and 16) a very large C-band was found occasionally in chromosomes 4, 5, 6, 11, 12, 14, and 15, and an unusual insertion of the Y chromosome was observed. A total of 128 C-band variants (6.89%) was found in the 1,857 Hiroshima residents. (author)
Advances in detection systems of gene and chromosome abnormalities
International Nuclear Information System (INIS)
Yatagai, Takeo
This review is described from the aspect of radiation biology. For analysis at gene level, oxidative lesion of DNA like 7,8-dihydro-8-oxoguanine formation and its repair by DNA polymerase η etc in bacteria, yeast and mammalian cells are suggested to be a useful index of radiation mutation. Transgenic mice with E. coli and/or phage gene as a reporter can be a tool for gene analysis for specific organ mutation: data obtained by irradiation of X-ray, γ-ray and accelerated carbon beam to the mouse gpt delta are presented. For analysis from gene to chromosome levels, loss of heterozygosity of a specific gene is a key for analysis of chromosome aberration at the molecular level. Studies in yeast and mammalian cells are presented. The author also described data of gene mutation in TK6 cells irradiated by 2 Gy of X-ray and 10 cGy of carbon beam (135 MeV/u) generated by ring-cycrotron. Human-hamster hybrid cell is an alternative tool. Concerning significance at the individual level, the author quoted studies of irradiation of parent mice resulting in increased incidence of somatic cell mutation and of cancer in offspring. Future systems for gene mutation will be a use of transgenic mice or of markers like a specific cancer. (K.H.)
Chromosomal localization of the human vesicular amine transporter genes
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Peter, D.; Finn, P.; Liu, Y.; Roghani, A.; Edwards, R.H.; Klisak, I.; Kojis, T.; Heinzmann, C.; Sparkes, R.S. (UCLA School of Medicine, Los Angeles, CA (United States))
The physiologic and behavioral effects of pharmacologic agents that interfere with the transport of monoamine neurotransmitters into vesicles suggest that vesicular amine transport may contribute to human neuropsychiatric disease. To determine whether an alteration in the genes that encode vesicular amine transport contributes to the inherited component of these disorders, the authors have isolated a human cDNA for the brain transporter and localized the human vesciular amine transporter genes. The human brain synaptic vesicle amine transporter (SVAT) shows unexpected conservation with rat SVAT in the regions that diverge extensively between rat SVAT and the rat adrenal chromaffin granule amine transporter (CGAT). Using the cloned sequences with a panel of mouse-human hybrids and in situ hybridization for regional localization, the adrenal CGAT gene (or VAT1) maps to human chromosome 8p21.3 and the brain SVAT gene (or VAT2) maps to chromosome 10q25. Both of these sites occur very close to if not within previously described deletions that produce severe but viable phenotypes. 26 refs., 3 figs., 1 tab.
A Wnt/beta-catenin pathway antagonist Chibby binds Cenexin at the distal end of mother centrioles and functions in primary cilia formation.
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Nathan Steere
Full Text Available The mother centriole of the centrosome is distinguished from immature daughter centrioles by the presence of accessory structures (distal and subdistal appendages, which play an important role in the organization of the primary cilium in quiescent cells. Primary cilia serve as sensory organelles, thus have been implicated in mediating intracellular signal transduction pathways. Here we report that Chibby (Cby, a highly conserved antagonist of the Wnt/β-catenin pathway, is a centriolar component specifically located at the distal end of the mother centriole and essential for assembly of the primary cilium. Cby appeared as a discrete dot in the middle of a ring-like structure revealed by staining with a distal appendage component of Cep164. Cby interacted with one of the appendage components, Cenexin (Cnx, which thereby abrogated the inhibitory effect of Cby on β-catenin-mediated transcriptional activation in a dose-dependent manner. Cby and Cnx did not precisely align, as Cby was detected at a more distal position than Cnx. Cnx emerged earlier than Cby during the cell cycle and was required for recruitment of Cby to the mother centriole. However, Cby was dispensable for Cnx localization to the centriole. During massive centriogenesis in in vitro cultured mouse tracheal epithelial cells, Cby and Cnx were expressed in a similar pattern, which was coincident with the expression of Foxj1. Our results suggest that Cby plays an important role in organization of both primary and motile cilia in collaboration with Cnx.
A Wnt/beta-catenin pathway antagonist Chibby binds Cenexin at the distal end of mother centrioles and functions in primary cilia formation.
Steere, Nathan; Chae, Vanessa; Burke, Michael; Li, Feng-Qian; Takemaru, Ken-ichi; Kuriyama, Ryoko
The mother centriole of the centrosome is distinguished from immature daughter centrioles by the presence of accessory structures (distal and subdistal appendages), which play an important role in the organization of the primary cilium in quiescent cells. Primary cilia serve as sensory organelles, thus have been implicated in mediating intracellular signal transduction pathways. Here we report that Chibby (Cby), a highly conserved antagonist of the Wnt/β-catenin pathway, is a centriolar component specifically located at the distal end of the mother centriole and essential for assembly of the primary cilium. Cby appeared as a discrete dot in the middle of a ring-like structure revealed by staining with a distal appendage component of Cep164. Cby interacted with one of the appendage components, Cenexin (Cnx), which thereby abrogated the inhibitory effect of Cby on β-catenin-mediated transcriptional activation in a dose-dependent manner. Cby and Cnx did not precisely align, as Cby was detected at a more distal position than Cnx. Cnx emerged earlier than Cby during the cell cycle and was required for recruitment of Cby to the mother centriole. However, Cby was dispensable for Cnx localization to the centriole. During massive centriogenesis in in vitro cultured mouse tracheal epithelial cells, Cby and Cnx were expressed in a similar pattern, which was coincident with the expression of Foxj1. Our results suggest that Cby plays an important role in organization of both primary and motile cilia in collaboration with Cnx.
Reprogramming to pluripotency can conceal somatic cell chromosomal instability.
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Masakazu Hamada
Full Text Available The discovery that somatic cells are reprogrammable to pluripotency by ectopic expression of a small subset of transcription factors has created great potential for the development of broadly applicable stem-cell-based therapies. One of the concerns regarding the safe use of induced pluripotent stem cells (iPSCs in therapeutic applications is loss of genomic integrity, a hallmark of various human conditions and diseases, including cancer. Structural chromosome defects such as short telomeres and double-strand breaks are known to limit reprogramming of somatic cells into iPSCs, but whether defects that cause whole-chromosome instability (W-CIN preclude reprogramming is unknown. Here we demonstrate, using aneuploidy-prone mouse embryonic fibroblasts (MEFs in which chromosome missegregation is driven by BubR1 or RanBP2 insufficiency, that W-CIN is not a barrier to reprogramming. Unexpectedly, the two W-CIN defects had contrasting effects on iPSC genomic integrity, with BubR1 hypomorphic MEFs almost exclusively yielding aneuploid iPSC clones and RanBP2 hypomorphic MEFs karyotypically normal iPSC clones. Moreover, BubR1-insufficient iPSC clones were karyotypically unstable, whereas RanBP2-insufficient iPSC clones were rather stable. These findings suggest that aneuploid cells can be selected for or against during reprogramming depending on the W-CIN gene defect and present the novel concept that somatic cell W-CIN can be concealed in the pluripotent state. Thus, karyotypic analysis of somatic cells of origin in addition to iPSC lines is necessary for safe application of reprogramming technology.
Complex chromosome rearrangements related 15q14 microdeletion plays a relevant role in phenotype expression and delineates a novel recurrent syndrome
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Tomaiuolo Anna
Full Text Available Abstract Complex chromosome rearrangements are constitutional structural rearrangements involving three or more chromosomes or having more than two breakpoints. These are rarely seen in the general population but their frequency should be much higher due to balanced states with no phenotypic presentation. These abnormalities preferentially occur de novo during spermatogenesis and are transmitted in families through oogenesis. Here, we report a de novo complex chromosome rearrangement that interests eight chromosomes in eighteen-year-old boy with an abnormal phenotype consisting in moderate developmental delay, cleft palate, and facial dysmorphisms. Standard G-banding revealed four apparently balanced traslocations involving the chromosomes 1;13, 3;19, 9;15 and 14;18 that appeared to be reciprocal. Array-based comparative genomic hybridization analysis showed no imbalances at all the breakpoints observed except for an interstitial microdeletion on chromosome 15. This deletion is 1.6 Mb in size and is located at chromosome band 15q14, distal to the Prader-Willi/Angelman region. Comparing the features of our patient with published reports of patients with 15q14 deletion this finding corresponds to the smallest genomic region of overlap. The deleted segment at 15q14 was investigated for gene content.
Chromosomal instability can be induced by the formation of breakage-prone chromosome rearrangement junctions
International Nuclear Information System (INIS)
Allen, R.N.; Ritter, L.; Moore, S.R.; Grosovsky, A.J.
Full text: Studies in our lab have led to the hypothesis that chromosomal rearrangements can generate novel breakage-prone sites, resulting in chromosomal instability acting predominantly in cis. For example, specific breakage of large blocks of centromeric region heterochromatin on chromosome 16q by treatment with 2,6-diaminopurine (DAP) is associated with repeated rearrangement of chromosome 16q during outgrowth of DAP-treated clones, thereby establishing a link between the initial site of damage and the occurrence of persistent chromosomal instability. Similarly, karyotypic analysis of gamma ray induced instability demonstrated that chromosomal rearrangements in sub-clones were significantly clustered near the site of previously identified chromosomal rearrangement junctions in unstable parental clones. This study investigates the hypothesis that integration of transfected sequences into host chromosomes could create breakage-prone junction regions and persistent genomic instability without exposure to DNA-damage agents. These junctions may mimic the unstable chromosomal rearrangements induced by DAP or radiation, and thus provide a test of the broader hypothesis that instability can to some extent be attributed to the formation of novel chromosomal breakage hot spots. These experiments were performed using human-hamster hybrid AL cells containing a single human chromosome 11, which was used to monitor instability in a chromosomal painting assay. AL cells were transfected with a 2.5 Kb fragment containing multiple copies of the 180 bp human alpha heterochromatic repeat, which resulted in chromosomal instability in 41% of the transfected clones. Parallel exposure to gamma-radiation resulted in a similar level of chromosomal instability, although control transfections with plasmid alone did not lead to karyotypic instability. Chromosomal instability induced by integration of alpha heterochromatic repeats was also frequently associated with delayed reproductive