Fluorescent in situ hybridization (FISH) allows the identification of the presence or absence of a specific region of DNA. A complementary DNA probe specific for the region in question is generated, and a fluorescent marker is attached. The probe is incubated with cells from the subject and viewed under a microscope. The bound probe fluoresces, allowing the number of copies of the DNA segment in question to be counted. This technique is useful in Prader-Willi syndrome and Angelman syndrome, in which a deletion in a segment of 15q11.2 occurs, and in velocardiofacial (DiGeorge) syndrome, which is associated with a deletion of 22q11.2.
Microarray comparative genomic hybridization (array CGH)has supplanted prophase analysis in cases in which a subtlechromosomal deletion or duplication (copy number variant) issuspected. In array CGH, DNA from the individual being studied and a normal control is labeled with fluorescent markers and hybridized to thousands of FISH-like probes for sequencesspread around the genome. The probes are derived from knowngenes and noncoding regions. By analyzing the ratio of intensityof the fluorescent marker at each site, it is possible to determinewhether the individual in question has any difference in copynumber compared with the control DNA.
Direct DNA analysis allows identification of mutations in a growing number of genetic disorders. Using polymerase chain reaction, the specific gene in question can be amplified and analyzed. The website www.genetests.org lists disorders in which direct DNA analysis is available and identifies laboratories performing such testing.
Errors that occur in meiosis during the production of gametes can lead to abnormalities of chromosome structure or number. Syndromes caused by chromosomal abnormalitiesinclude trisomy 21 (Down syndrome or DS), trisomy 13, trisomy 18, Turner syndrome (TS), and Klinefelter syndrome (KS), as well as rarer chromosomal duplications, deletions, or inversions.
Chromosomal abnormalities occur in approximately 8% of fertilized ova but in only 0.6% of liveborn infants. Fifty percent of spontaneous abortuses have chromosomal abnormalities, the most common being 45,X (TS); an estimated 99% of 45,X fetuses are spontaneously aborted. The fetal loss rate for DS, the most viable of the autosomal aneuploidies, approaches 80%. Most other chromosomal abnormalities also adversely affect fetal viability. In newborns and older children, features that suggest the presence of a chromosome anomaly include low birth weight (small for gestational age), failure to thrive, developmental delay, and the presence of three or more congenital malformations.
During meiosis or mitosis, failure of a chromosomal pair to separate properly results in nondisjunction. Aneuploidy is a change in the number of chromosomes that results from non-disjunction. A cell may have one (monosomy) or three (trisomy) copies of a particular chromosome.
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