Genome-wide patterns and properties of de novo mutations in humans
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Author
Francioli, Laurent C.
Polak, Paz P.
Menelaou, Androniki
Renkens, Ivo
van Duijn, Cornelia M.
Swertz, Morris
Wijmenga, Cisca
van Ommen, Gertjan
Slagboom, P. Eline
Boomsma, Dorret I.
Ye, Kai
Guryev, Victor
Arndt, Peter F.
Kloosterman, Wigard P.
de Bakker, Paul I. W.
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1038/ng.3292Metadata
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Francioli, L. C., P. P. Polak, A. Koren, A. Menelaou, S. Chun, I. Renkens, C. M. van Duijn, et al. 2015. “Genome-wide patterns and properties of de novo mutations in humans.” Nature genetics 47 (7): 822-826. doi:10.1038/ng.3292. http://dx.doi.org/10.1038/ng.3292.Abstract
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 whole-genomes of 250 families. We show that de novo mutations in 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 reveal signatures of transcription-coupled repair, while mutation clusters with a unique signature point to a novel mutational mechanism. Mutation and recombination rates independently associate with nucleotide diversity, and regional variation in human-chimpanzee divergence is only partly explained by mutation rate heterogeneity. Finally, we provide a genome-wide mutation rate map for medical and population genetics applications. Our results reveal novel insights and refine long-standing hypotheses about human mutagenesis.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4485564/pdf/Terms of Use
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http://nrs.harvard.edu/urn-3:HUL.InstRepos:24983850
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