Multi-nucleotide de novo Mutations in Humans.

Mutation of the DNA molecule is one of the most fundamental processes in biology. In this study, we use 283 parent-offspring trios to estimate the rate of mutation for both single nucleotide variants (SNVs) and short length variants (indels) in humans and examine the mutation process. We found 17812 SNVs, corresponding to a mutation rate of 1.29 × 10-8 per position per generation (PPPG) and 1282 indels corresponding to a rate of 9.29 × 10-10 PPPG. We estimate that around 3% of human de novo SNVs are part of a multi-nucleotide mutation (MNM), with 558 (3.1%) of mutations positioned less than 20kb from another mutation in the same individual (median distance of 525bp). The rate of de novo mutations is greater in late replicating regions (p = 8.29 × 10-19) and nearer recombination events (p = 0.0038) than elsewhere in the genome.