Mechanisms and consequences of somatic mosaicism in humans

Mechanisms of mosaicism (the presence of genetically distinct populations of cells in a given organism) include DNA structural abnormalities, epigenetic changes, and the abnormal distribution of chromosomes and mitochondria in daughter cells. Somatic and germ-line mosaicism can coexist in an individual. Several, otherwise lethal, genetic mutations are revealed only in the somatic mosaic state. The Bloom syndrome helicase and the mismatch-repair system are important in the generation of somatic genetic variability. Spontaneous reversions of inherited mutations can occur by homologous recombination, site-specific correction and second-site suppressor mutations. The extent of somatic mosaicism is determined most crucially by selection. Treatment of a genetic disorder can influence the degree of mosaicism and the frequency or maintenance of reverted cell populations.