Rate of de novo mutations and the importance of father's age to disease risk.

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. Mutations generate sequence diversity and provide a substrate for selection. The rate of de novo mutations is therefore of major importance to evolution. Here we conduct a study of genome-...

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Bibliographic Details
Published in:Nature
Main Authors: Kong, Augustine, Frigge, Michael L, Masson, Gisli, Besenbacher, Soren, Sulem, Patrick, Magnusson, Gisli, Gudjonsson, Sigurjon A, Sigurdsson, Asgeir, Jonasdottir, Aslaug, Jonasdottir, Adalbjorg, Wong, Wendy S W, Sigurdsson, Gunnar, Walters, G Bragi, Steinberg, Stacy, Helgason, Hannes, Thorleifsson, Gudmar, Gudbjartsson, Daniel F, Helgason, Agnar, Magnusson, Olafur Th, Thorsteinsdottir, Unnur, Stefansson, Kari
Other Authors: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland.
Format: Article in Journal/Newspaper
Language:English
Published: Nature Publishing Group 2013
Subjects:
Adult
Autistic Disorder
Chromosomes
Human
Female
Genetic Predisposition to Disease
Genome
Humans
Iceland
Male
Middle Aged
Mothers
Mutation Rate
Ovum
Paternal Age
Pedigree
Polymorphism
Single Nucleotide
Risk Factors
Schizophrenia
Selection
Genetic
Sequence Analysis
DNA
Spermatozoa
Young Adult
Online Access:http://hdl.handle.net/2336/300227
https://doi.org/10.1038/nature11396
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Summary:To access publisher full text version of this article. Please click on the hyperlink in Additional Links field. Mutations generate sequence diversity and provide a substrate for selection. The rate of de novo mutations is therefore of major importance to evolution. Here we conduct a study of genome-wide mutation rates by sequencing the entire genomes of 78 Icelandic parent-offspring trios at high coverage. We show that in our samples, with an average father's age of 29.7, the average de novo mutation rate is 1.20 × 10(-8) per nucleotide per generation. Most notably, the diversity in mutation rate of single nucleotide polymorphisms is dominated by the age of the father at conception of the child. The effect is an increase of about two mutations per year. An exponential model estimates paternal mutations doubling every 16.5 years. After accounting for random Poisson variation, father's age is estimated to explain nearly all of the remaining variation in the de novo mutation counts. These observations shed light on the importance of the father's age on the risk of diseases such as schizophrenia and autism. National Institutes of Health MH071425 info:eu-repo/grantAgreement/EC/FP7/223423 IAPP-MC-251592 European Community IMI grant EU-AIMS 115300

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