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

Augustine Kong (), Michael L. Frigge, Gisli Masson, Soren Besenbacher, Patrick Sulem, Gisli Magnusson, Sigurjon A. Gudjonsson, Asgeir Sigurdsson, Aslaug Jonasdottir, Adalbjorg Jonasdottir, Wendy S. W. Wong, Gunnar Sigurdsson, G. Bragi Walters, Stacy Steinberg, Hannes Helgason, Gudmar Thorleifsson, Daniel F. Gudbjartsson, Agnar Helgason, Olafur Th. Magnusson, Unnur Thorsteinsdottir and Kari Stefansson ()
Additional contact information
Augustine Kong: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Michael L. Frigge: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Gisli Masson: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Soren Besenbacher: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Patrick Sulem: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Gisli Magnusson: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Sigurjon A. Gudjonsson: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Asgeir Sigurdsson: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Aslaug Jonasdottir: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Adalbjorg Jonasdottir: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Wendy S. W. Wong: Illumina Cambridge Ltd, Chesterford Research Park, Little Chesterford, Essex CB10 1XL, UK
Gunnar Sigurdsson: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
G. Bragi Walters: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Stacy Steinberg: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Hannes Helgason: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Gudmar Thorleifsson: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Daniel F. Gudbjartsson: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Agnar Helgason: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Olafur Th. Magnusson: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Unnur Thorsteinsdottir: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland
Kari Stefansson: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland

Nature, 2012, vol. 488, issue 7412, 471-475

Abstract: Abstract 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.

Date: 2012
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DOI: 10.1038/nature11396

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