Faculty, Staff and Student Publications
Publication Date
2-4-2020
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abstract
De novo mutations (DNMs), or mutations that appear in an individual despite not being seen in their parents, are an important source of genetic variation whose impact is relevant to studies of human evolution, genetics, and disease. Utilizing high-coverage whole-genome sequencing data as part of the Trans-Omics for Precision Medicine (TOPMed) Program, we called 93,325 single-nucleotide DNMs across 1,465 trios from an array of diverse human populations, and used them to directly estimate and analyze DNM counts, rates, and spectra. We find a significant positive correlation between local recombination rate and local DNM rate, and that DNM rate explains a substantial portion (8.98 to 34.92%, depending on the model) of the genome-wide variation in population-level genetic variation from 41K unrelated toPMed samples. Genome-wide heterozygosity does correlate with DNM rate, but only explains
Keywords
Adult, Amish, Cohort Studies, DNA Mutational Analysis, Female, Genetics, Population, Genome, Human, Heterozygote, Humans, Male, Mutation, Pedigree, Whole Genome Sequencing, Young Adult
DOI
10.1073/pnas.1902766117
PMID
31964835
PMCID
PMC7007577
PubMedCentral® Posted Date
January 2020
PubMedCentral® Full Text Version
Post-print