Estimating the human mutation rate using autozygosity in a founder population

Catarina D. Campbell, Jessica X. Chong, Maika Malig, Arthur Ko, Beth L. Dumont, Lide Han, Laura Vives, Brian J. O'Roak, Peter H. Sudmant, Jay Shendure, Mark Abney, Carole Ober, Evan E. Eichler

Research output: Contribution to journalArticlepeer-review

160 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1277-1281
Number of pages5
JournalNature genetics
Issue number11
StatePublished - Nov 2012
Externally publishedYes

ASJC Scopus subject areas

  • Genetics


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