In:
PLOS Genetics, Public Library of Science (PLoS), Vol. 18, No. 9 ( 2022-9-19), p. e1010404-
Abstract:
Most somatic mutations that arise during normal development are present at low levels in single or multiple tissues depending on the developmental stage and affected organs. However, the effect of human developmental stages or mutations of different organs on the features of somatic mutations is still unclear. Here, we performed a systemic and comprehensive analysis of low-level somatic mutations using deep whole-exome sequencing (average read depth ~500×) of 498 multiple organ tissues with matched controls from 190 individuals. Our results showed that early clone-forming mutations shared between multiple organs were lower in number but showed higher allele frequencies than late clone-forming mutations [0.54 vs. 5.83 variants per individual; 6.17% vs. 1.5% variant allele frequency (VAF)] along with less nonsynonymous mutations and lower functional impacts. Additionally, early and late clone-forming mutations had unique mutational signatures that were distinct from mutations that originated from tumors. Compared with early clone-forming mutations that showed a clock-like signature across all organs or tissues studied, late clone-forming mutations showed organ, tissue, and cell-type specificity in the mutation counts, VAFs, and mutational signatures. In particular, analysis of brain somatic mutations showed a bimodal occurrence and temporal-lobe-specific signature. These findings provide new insights into the features of somatic mosaicism that are dependent on developmental stage and brain regions.
Type of Medium:
Online Resource
ISSN:
1553-7404
DOI:
10.1371/journal.pgen.1010404
DOI:
10.1371/journal.pgen.1010404.g001
DOI:
10.1371/journal.pgen.1010404.g002
DOI:
10.1371/journal.pgen.1010404.g003
DOI:
10.1371/journal.pgen.1010404.g004
DOI:
10.1371/journal.pgen.1010404.s001
DOI:
10.1371/journal.pgen.1010404.s002
DOI:
10.1371/journal.pgen.1010404.s003
DOI:
10.1371/journal.pgen.1010404.s004
DOI:
10.1371/journal.pgen.1010404.s005
DOI:
10.1371/journal.pgen.1010404.r001
DOI:
10.1371/journal.pgen.1010404.r002
DOI:
10.1371/journal.pgen.1010404.r003
DOI:
10.1371/journal.pgen.1010404.r004
DOI:
10.1371/journal.pgen.1010404.r005
DOI:
10.1371/journal.pgen.1010404.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2186725-2
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