Publication Date
10-1-2024
Journal
Nature Reviews Genetics
DOI
10.1038/s41576-024-00715-z
PMID
38605218
PMCID
PMC11408116
PubMedCentral® Posted Date
4-1-2025
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Mosaicism, Humans, Embryonic Development, Animals, Embryo, Mammalian, Genetic Diseases, Inborn, Mutation
Abstract
Nearly every mammalian cell division is accompanied by a mutational event that becomes fixed in a daughter cell. When carried forward to additional cell progeny, a clone of variant cells can emerge. As a result, mammals are complex mosaics of clones that are genetically distinct from one another. Recent high-throughput sequencing studies have revealed that mosaicism is common, clone sizes often increase with age and specific variants can affect tissue function and disease development. Variants that are acquired during early embryogenesis are shared by multiple cell types and can affect numerous tissues. Within tissues, variant clones compete, which can result in their expansion or elimination. Embryonic mosaicism has clinical implications for genetic disease severity and transmission but is likely an under-recognized phenomenon. To better understand its implications for mosaic individuals, it is essential to leverage research tools that can elucidate the mechanisms by which expanded embryonic variants influence development and disease.