Genetic variation across and within individuals

Nat Rev Genet. 2024 Aug;25(8):548-562. doi: 10.1038/s41576-024-00709-x. Epub 2024 Mar 28.

Abstract

Germline variation and somatic mutation are intricately connected and together shape human traits and disease risks. Germline variants are present from conception, but they vary between individuals and accumulate over generations. By contrast, somatic mutations accumulate throughout life in a mosaic manner within an individual due to intrinsic and extrinsic sources of mutations and selection pressures acting on cells. Recent advancements, such as improved detection methods and increased resources for association studies, have drastically expanded our ability to investigate germline and somatic genetic variation and compare underlying mutational processes. A better understanding of the similarities and differences in the types, rates and patterns of germline and somatic variants, as well as their interplay, will help elucidate the mechanisms underlying their distinct yet interlinked roles in human health and biology.

Publication types

  • Review

MeSH terms

  • Genetic Predisposition to Disease
  • Genetic Variation*
  • Germ-Line Mutation*
  • Humans
  • Mutation