17/06/2016 Biology
DOI: 10.1101/059436 SemanticScholar ID: 89129663 MAG: 2427603609

A direct multi-generational estimate of the human mutation rate from autozygous segments seen in thousands of parentally related individuals

Publication Summary

Heterozygous mutations within homozygous sequences descended from a recent common ancestor offer a way to ascertain de novo mutations (DNMs) across multiple generations. Using exome sequences from 3,222 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 noncrossover 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 germline mutation rate. We found frequent recurrence of mutations at polymorphic CpG sites, and an increase in C to T mutations in a 5’ CCG 3’ → 5’ CTG 3’ context in the Pakistani population compared to Europeans, suggesting that mutational processes have evolved rapidly between human populations.

CAER Authors

Avatar Image for John Wright

Prof. John Wright

Bradford Institute for Health Research - Chief Investigator Born in Bradford

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