How much of the variation in the mutation rate along the human genome can be explained?

• Published in: G3 : genes - genomes - genetics Vol. 4; no. 9; pp. 1667 - 1670
• Main Authors: Eyre-Walker, Adam, Eyre-Walker, Ying Chen
• Format: Journal Article
• Language: English
• Published: United States Genetics Society of America 01.09.2014
• Subjects: CpG Islands; Genome, Human - genetics; Humans; Investigations; Models, Genetic; Mutation Rate; Polymorphism, Single Nucleotide; cryptic variation; human mutation; de novo mutation; mutation rate variation; mutation rate
• ISSN: 2160-1836; 2160-1836
• DOI: 10.1534/g3.114.012849

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.