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Journal Article

Genome-wide patterns and properties of de novo mutations in humans

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons50074

Arndt,  P. F.
Evolutionary Genomics (Peter Arndt), Dept. of Computational Molecular Biology (Head: Martin Vingron), Max Planck Institute for Molecular Genetics, Max Planck Society;

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Citation

Francioli, L. C., Polak, P. P., Koren, A., Menelaou, A., Chun, S., Renkens, I., 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.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002A-4F25-6
Abstract
Mutations create variation in the population, fuel evolution and cause genetic diseases. Current knowledge about de novo mutations is incomplete and mostly indirect. 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 but also occur more frequently in early-replicating, genic regions. Functional regions exhibit higher mutation rates due to CpG dinucleotides and show signatures of transcription-coupled 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.