special subjects
DNA Variants and Mutations
Mosaicism
Mosaicism occurs when A person starting from a single fertilized egg develops≥2 cell lines differing in genotype Mosaicism is a normal consequence of Chromosomal inactivation in females; in most females, some cells have an inactive maternal X, and other cells have an inactive paternal X. Mosaicism can also result from mutations. Mutations are likely to occur during cell division in any large multicellular organism; each time a cell divides, 4 or 5 changes are estimated to occur in the DNA. Because these changes can be passed on to subsequently produced cells, large multicellular organisms have subclones of cells that have slightly different genotypes. Mosaicism may be recognized as the cause of disorders in which patchy changes occur. For example, McCune-Albright syndrome is associated with patchy dysplastic changes in the bone, endocrine gland abnormalities, patchy pigmentary changes, and occasionally heart or liver abnormalities. Occurrence of the McCune-Albright mutation in all cells would cause early death; however, people with mosaicism survive because normal tissue supports the abnormal tissue. Occasionally, a parent with a Single-Gene Defects seems to have a mild form but actually represents a mosaic; the parent’s offspring is more severely affected if they receive a germ cell with the mutant allele and thus have the abnormality in every cell. Overview of Chromosomal Abnormalities are most often fatal to the fetus. However, chromosomal mosaicism occurs in some embryos, resulting in some chromosomally normal cells, which can allow offspring to be born alive. Chromosomal mosaicism can be detected with prenatal genetic testing, particularly chorionic villus sampling. 