title: How much of the variation in the mutation rate along the human genome can be explained?
abstract: It has been claimed recently that it may be possible to predict the rate of de novo mutation of each site in the human genome with a high degree of accuracy [Michaelson et al. (2012), Cell 151: 1431-1442]. We show that this claim is unwarranted. By considering the correlation between the rate of de novo mutation and the predictions from the model of Michaelson et al., we show there could be substantial unexplained variance in the mutation rate. We investigate whether the model of Michaelson et al. captures variation at the single nucleotide level that is not due to simple context. We show that the model captures a substantial fraction of this variation at CpG dinucleotides but fails to explain much of the variation at non-CpG sites.
authors.affiliation: School of Life Sciences, University of Sussex, Brighton, BN1 9QG, United Kingdom a.c.eyre-walker@sussex.ac.uk.
authors.forename: Adam
authors.identifier: http://orcid.org/0000-0001-5527-8729
authors.initials: A
authors.lastname: Eyre-Walker
authors.affiliation: School of Life Sciences, University of Sussex, Brighton, BN1 9QG, United Kingdom.
authors.forename: Ying Chen
authors.initials: YC
authors.lastname: Eyre-Walker
mesh_terms: D018899:CpG Islands; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D008957:Models, Genetic; D059645:Mutation Rate; D020641:Polymorphism, Single Nucleotide
keywords: cryptic variation; de novo mutation; human mutation; mutation rate; mutation rate variation