Mosaicism in Human Health and Disease

• Published in: Annual review of genetics Vol. 54; no. 1; pp. 487 - 510
• Main Authors: Thorpe, Jeremy, Osei-Owusu, Ikeoluwa A, Avigdor, Bracha Erlanger, Tupler, Rossella, Pevsner, Jonathan
• Format: Journal Article
• Language: English
• Published: United States Annual Reviews 23.11.2020; Annual Reviews, Inc
• Subjects: Chromosomes; Deoxyribonucleic acid; Developmental stages; DNA; Epigenetics; Genomes; Genomic imprinting; germline mutation; Gonads; Heteroplasmy; Inactivation; Mitochondrial DNA; mosaic aneuploidy; Mosaicism; Mutation; Next-generation sequencing; Offspring; somatic mutation; X-chromosome inactivation; somatic mutation; germline mutation; mosaic aneuploidy; mosaicism
• ISSN: 0066-4197; 1545-2948
• DOI: 10.1146/annurev-genet-041720-093403

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.