Journal
NATURE GENETICS
Volume 47, Issue 7, Pages 822-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/ng.3292
Keywords
-
Categories
Funding
- Biobanking and Biomolecular Research Infrastructure (BBMRI-NL)
- Netherlands Organization for Scientific Research (NWO project) [184.021.007]
- US National Institutes of Health [1 R01 MH101244, 1 R01 GM078598]
Ask authors/readers for more resources
Mutations create variation in the population, fuel evolution and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect(1-10). Here we analyze 11,020 de novo mutations from the whole genomes of 250 families. We show that de novo mutations in the offspring of older fathers are not only more numerous(11-13) but also occur more frequently in early-replicating, genic regions. Functional regions exhibit higher mutation rates due to CpG dinucleotides and show signatures of transcriptioncoupled repair, whereas mutation clusters with a unique signature point to a new mutational mechanism. Mutation and recombination rates independently associate with nucleotide diversity, and regional variation in human-chimpanzee divergence is only partly explained by heterogeneity in mutation rate. Finally, we provide a genome-wide mutation rate map for medical and population genetics applications. Our results provide new insights and refine long-standing hypotheses about human mutagenesis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available