|Title||Estimating the human mutation rate using autozygosity in a founder population|
|Publication Type||Journal Article|
|Year of Publication||2012|
|Authors||Campbell, CD, Chong, JX, Malig, M, Ko, A, Dumont, BL, Han, L, Vives, L, O'Roak, BJ, Sudmant, PH, Shendure, J, Abney, M, Ober, C, Eichler, EE|
|Pagination||1277 - 1281|
|Keywords||fitness effects, founder effect, Hutterites, life history, mutation rate, paternal age|
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.
|Short Title||Nat Genet|
Estimating the human mutation rate using autozygosity in a founder population
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