title: Multi-nucleotide de novo Mutations in Humans.
abstract: Mutation of the DNA molecule is one of the most fundamental processes in biology. In this study, we use 283 parent-offspring trios to estimate the rate of mutation for both single nucleotide variants (SNVs) and short length variants (indels) in humans and examine the mutation process. We found 17812 SNVs, corresponding to a mutation rate of 1.29 × 10-8 per position per generation (PPPG) and 1282 indels corresponding to a rate of 9.29 × 10-10 PPPG. We estimate that around 3% of human de novo SNVs are part of a multi-nucleotide mutation (MNM), with 558 (3.1%) of mutations positioned less than 20kb from another mutation in the same individual (median distance of 525bp). The rate of de novo mutations is greater in late replicating regions (p = 8.29 × 10-19) and nearer recombination events (p = 0.0038) than elsewhere in the genome.
authors.affiliation: Department of Molecular Medicine, Aarhus University, Denmark.
authors.forename: Søren
authors.identifier: http://orcid.org/0000-0003-1455-1738
authors.initials: S
authors.lastname: Besenbacher
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulem
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.|Department of Anthropology, University of Iceland, Iceland.
authors.forename: Agnar
authors.initials: A
authors.lastname: Helgason
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.|School of Engineering and Natural Sciences, University of Iceland, Iceland.
authors.forename: Hannes
authors.initials: H
authors.lastname: Helgason
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.
authors.forename: Helgi
authors.initials: H
authors.lastname: Kristjansson
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.
authors.forename: Aslaug
authors.initials: A
authors.lastname: Jonasdottir
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.
authors.forename: Adalbjorg
authors.initials: A
authors.lastname: Jonasdottir
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.
authors.forename: Olafur Th
authors.initials: OT
authors.lastname: Magnusson
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.|Faculty of Medicine, University of Iceland, Iceland.
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.
authors.forename: Gisli
authors.initials: G
authors.lastname: Masson
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.|School of Engineering and Natural Sciences, University of Iceland, Iceland.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.affiliation: deCODE genetics/Amgen, Inc., Iceland.|Faculty of Medicine, University of Iceland, Iceland.
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D004252:DNA Mutational Analysis; D015894:Genome, Human; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D059645:Mutation Rate; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011995:Recombination, Genetic / Q000235:genetics