Estimating the human mutation rate from autozygous segments reveals population differences in human mutational processes

Vagheesh M. Narasimhan*, Raheleh Rahbari, Aylwyn Scally, Arthur Wuster, Dan Mason, Yali Xue, John Wright, Richard C. Trembath, Eamonn R. Maher, David A. Van Heel, Adam Auton, Matthew E. Hurles, Chris Tyler-Smith, Richard Durbin

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)
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Abstract

Heterozygous mutations within homozygous sequences descended from a recent common ancestor offer a way to ascertain de novo mutations across multiple generations. Using exome sequences from 3222 British-Pakistani individuals with high parental relatedness, we estimate a mutation rate of 1.45 ± 0.05 × 10-8 per base pair per generation in autosomal coding sequence, with a corresponding non-crossover gene conversion rate of 8.75 ± 0.05 × 10-6 per base pair per generation. This is at the lower end of exome mutation rates previously estimated in parent-offspring trios, suggesting that post-zygotic mutations contribute little to the human germ-line mutation rate. We find frequent recurrence of mutations at polymorphic CpG sites, and an increase in C to T mutations in a 5′ CCG 3′ to 5′ CTG 3′ context in the Pakistani population compared to Europeans, suggesting that mutational processes have evolved rapidly between human populations.

Original languageEnglish
Article number303
JournalNature Communications
Volume8
Issue number1
Early online date21 Aug 2017
DOIs
Publication statusPublished - 21 Aug 2017

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