A number of different methods have converged on the 1.2x10-8 mutation rate, or slightly slower/faster rates around this value. In the current paper, the authors exploited inbreeding within the Hutterite population to identify segments of autozygous DNA, i.e., chunks of DNA where the two copies in an individual were inherited from the same ancestor, but via different genealogical paths. These copies are nearly-identical, but not entirely so, since they followed different sequences of meioses in different bodies on their way from the common ancestor to the modern individuals. By counting these differences and dividing by the number of intervening meioses, an estimate of the mutation rate can be arrived at.
Nature Genetics 44, 1277–1281 (2012) doi:10.1038/ng.2418
Estimating the human mutation rate using autozygosity in a founder population
Catarina D Campbell et al.
Knowledge of the rate and pattern of new mutation is critical to the understanding of human disease and evolution. We used extensive autozygosity in a genealogically well-defined population of Hutterites to estimate the human sequence mutation rate over multiple generations. We sequenced whole genomes from 5 parent-offspring trios and identified 44 segments of autozygosity. Using the number of meioses separating each pair of autozygous alleles and the 72 validated heterozygous single-nucleotide variants (SNVs) from 512 Mb of autozygous DNA, we obtained an SNV mutation rate of 1.20 × 10−8 (95% confidence interval 0.89–1.43 × 10−8) mutations per base pair per generation. The mutation rate for bases within CpG dinucleotides (9.72 × 10−8) was 9.5-fold that of non-CpG bases, and there was strong evidence (P = 2.67 × 10−4) for a paternal bias in the origin of new mutations (85% paternal). We observed a non-uniform distribution of heterozygous SNVs (both newly identified and known) in the autozygous segments (P = 0.001), which is suggestive of mutational hotspots or sites of long-range gene conversion.