Pathogenic Mechanisms of Somatic Mutation and Genome Mosaicism in Aging

Jan Vijg, Xiao Dong

Research output: Contribution to journalReview articlepeer-review

33 Scopus citations

Abstract

Age-related accumulation of postzygotic DNA mutations results in tissue genetic heterogeneity known as somatic mosaicism. Although implicated in aging as early as the 1950s, somatic mutations in normal tissue have been difficult to study because of their low allele fractions. With the recent emergence of cost-effective high-throughput sequencing down to the single-cell level, enormous progress has been made in our capability to quantitatively analyze somatic mutations in human tissue in relation to aging and disease. Here we first review how recent technological progress has opened up this field, providing the first broad sets of quantitative information on somatic mutations in vivo necessary to gain insight into their possible causal role in human aging and disease. We then propose three major mechanisms that can lead from accumulated de novo mutations across tissues to cell functional loss and human disease.

Original languageEnglish (US)
Pages (from-to)12-23
Number of pages12
JournalCell
Volume182
Issue number1
DOIs
StatePublished - Jul 9 2020

Bibliographical note

Funding Information:
This work was supported by the NIH (grants P01 AG017242, P01 AG047200, P30 AG038072, and U01 ES029519 to J.V. and K99 AG056656 to X.D.), the Glenn Foundation for Medical Research (to J.V.), and the Shanghai Jiao Tong University School of Medicine. J.V. and X.D. are co-founders and shareholders of SingulOmics Corp.

Funding Information:
This work was supported by the NIH (grants P01 AG017242 , P01 AG047200 , P30 AG038072 , and U01 ES029519 to J.V. and K99 AG056656 to X.D.), the Glenn Foundation for Medical Research (to J.V.), and the Shanghai Jiao Tong University School of Medicine .

Publisher Copyright:
© 2020 Elsevier Inc.

Keywords

  • age-related disease
  • aging
  • genome mosaicism
  • pathogenic effects
  • somatic DNA mutation
  • transcriptional noise

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

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