You are here

Science DOI:10.1126/science.aba7408

Population sequencing data reveal a compendium of mutational processes in the human germ line.

Publication TypeJournal Article
Year of Publication2021
AuthorsSeplyarskiy, VB, Soldatov, RA, Koch, E, McGinty, RJ, Goldmann, JM, Hernandez, RD, Barnes, K, Correa, A, Burchard, EG, Ellinor, PT, McGarvey, ST, Mitchell, BD, Vasan, RS, Redline, S, Silverman, E, Weiss, ST, Arnett, DK, Blangero, J, Boerwinkle, E, He, J, Montgomery, C, Rao, DC, Rotter, JI, Taylor, KD, Brody, JA, Chen, Y-DIda, Fuentes, Lde Las, Hwu, C-M, Rich, SS, Manichaikul, AW, Mychaleckyj, JC, Palmer, ND, Smith, JA, Kardia, SLR, Peyser, PA, Bielak, LF, O'Connor, TD, Emery, LS, Gilissen, C, Wong, WSW, Kharchenko, PV, Sunyaev, S
Corporate AuthorsNHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium, TOPMed Population Genetics Working Group
JournalScience
Volume373
Issue6558
Pages1030-1035
Date Published2021 Aug 27
ISSN1095-9203
Abstract

Biological mechanisms underlying human germline mutations remain largely unknown. We statistically decompose variation in the rate and spectra of mutations along the genome using volume-regularized nonnegative matrix factorization. The analysis of a sequencing dataset (TOPMed) reveals nine processes that explain the variation in mutation properties between loci. We provide a biological interpretation for seven of these processes. We associate one process with bulky DNA lesions that are resolved asymmetrically with respect to transcription and replication. Two processes track direction of replication fork and replication timing, respectively. We identify a mutagenic effect of active demethylation primarily acting in regulatory regions and a mutagenic effect of long interspersed nuclear elements. We localize a mutagenic process specific to oocytes from population sequencing data. This process appears transcriptionally asymmetric.

DOI10.1126/science.aba7408
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/34385354?dopt=Abstract

Alternate JournalScience
PubMed ID34385354