Mosaicism in Human Health and Disease

Mosaicism refers to the occurrence of two or more genomes in an individual derived from a single zygote. Germline mosaicism is a mutation that is limited to the gonads and can be transmitted to offspring. Somatic mosaicism is a postzygotic mutation that occurs in the soma, and it may occur at any developmental stage or in adult tissues. Mosaic variation may be classified in six ways: ( a ) germline or somatic origin, ( b ) class of DNA mutation (ranging in scale from single base pairs to multiple chromosomes), ( c ) developmental context, ( d ) body location(s), ( e ) functional consequence (including deleterious, neutral, or advantageous), and ( f ) additional sources of mosaicism, including mitochondrial heteroplasmy, exogenous DNA sources such as vectors, and epigenetic changes such as imprinting and X-chromosome inactivation. Technological advances, including single-cell and other next-generation sequencing, have facilitated improved sensitivity and specificity to detect mosaicism in a variety of biological contexts.