期刊
NATURE GENETICS
卷 44, 期 11, 页码 1277-1281出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.2418
关键词
-
资金
- US National Institutes of Health (NIH) Ruth L. Kirschstein National Research Service Award (NRSA) [F32HG006070]
- Howard Hughes Medical Institute
- American Asthma Foundation
- US NIH [R01 HD21244, R01 HL085197, R01 HG002899]
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 x 10(-8) (95% confidence interval 0.89-1.43 x 10(-8)) mutations per base pair per generation. The mutation rate for bases within CpG dinucleotides (9.72 x 10(-8)) was 9.5-fold that of non-CpG bases, and there was strong evidence (P = 2.67 x 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据