Estimating the human mutation rate from autozygous segments reveals population differences in human mutational processes
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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.
AuthorsNarasimhan, VM; Rahbari, R; Scally, A; Wuster, A; Mason, D; Xue, Y; Wright, J; Trembath, RC; Maher, ER; Van Heel, DA; Auton, A; Hurles, ME; Tyler-Smith, C; Durbin, R
- Genomic Medicine