RT Journal Article SR Electronic T1 A direct multi-generational estimate of the human mutation rate from autozygous segments seen in thousands of parentally related individuals JF bioRxiv FD Cold Spring Harbor Laboratory SP 059436 DO 10.1101/059436 A1 Vagheesh M Narasimhan A1 Raheleh Rahbari A1 Aylwyn Scally A1 Arthur Wuster A1 Dan Mason A1 Yali Xue A1 John Wright A1 Richard C Trembath A1 Eamonn R Maher A1 David A van Heel A1 Adam Auton A1 Matthew E Hurles A1 Chris Tyler-Smith A1 Richard Durbin YR 2016 UL http://biorxiv.org/content/early/2016/06/17/059436.abstract AB 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.