Estimating the human mutation rate from autozygous segments reveals population differences in human mutational processes.
Estimating the human mutation rate from autozygous segments reveals population differences in human mutational processes.
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估计自载段的人类突变率揭示了人类突变过程中的人口差异。
DOI：
10.1038/s41467-017-00323-y
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发表时间：
2017-08-21
影响因子：
16.6
通讯作者：
Durbin R
中科院分区：
文献类型：
--
作者：
Narasimhan VM;Rahbari R;Scally A;Wuster A;Mason D;Xue Y;Wright J;Trembath RC;Maher ER;van Heel DA;Auton A;Hurles ME;Tyler-Smith C;Durbin R
来自最近共同祖先的纯合序列中的杂合突变提供了一种确定多代从头突变的方法。利用3222名亲本亲缘关系高的英裔巴基斯坦人的外显子组序列，我们估计常染色体编码序列每代每碱基对的突变率为1.45±0.05 × 10−8，相应的非交叉基因转换率为每代每碱基对8.75±0.05 × 10−6。这是以前在父母-后代三胞胎中估计的外显子组突变率的低端，这表明合子后突变对人类种系突变率的贡献很小。我们发现多态性CpG位点突变频繁复发，与欧洲人相比，巴基斯坦人群中5′CCG 3′到5′CTG 3′的C到T突变增加，这表明突变过程在人群之间迅速进化。不同的方法对人类突变率的估计差异很大。在这里，作者提出了来自非欧洲人群的自合子部分的多代估计，从而深入了解了合子后突变和群体特异性突变过程的贡献。
Heterozygous mutations within homozygous sequences descended from a recent common ancestor offer a way to ascertain de novo mutations across multiple generations. Using exome sequences from 3222 British-Pakistani individuals with high parental relatedness, we estimate a mutation rate of 1.45 ± 0.05 × 10−8 per base pair per generation in autosomal coding sequence, with a corresponding non-crossover gene conversion rate of 8.75 ± 0.05 × 10−6 per base pair per generation. This is at the lower end of exome mutation rates previously estimated in parent–offspring trios, suggesting that post-zygotic mutations contribute little to the human germ-line mutation rate. We find frequent recurrence of mutations at polymorphic CpG sites, and an increase in C to T mutations in a 5ʹ CCG 3ʹ to 5ʹ CTG 3ʹ context in the Pakistani population compared to Europeans, suggesting that mutational processes have evolved rapidly between human populations. Estimates of human mutation rates differ substantially based on the approach. Here, the authors present a multi-generational estimate from the autozygous segment in a non-European population that gives insight into the contribution of post-zygotic mutations and population-specific mutational processes.
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影响因子：
64.8
作者：
Kong A;Frigge ML;Masson G;Besenbacher S;Sulem P;Magnusson G;Gudjonsson SA;Sigurdsson A;Jonasdottir A;Jonasdottir A;Wong WS;Sigurdsson G;Walters GB;Steinberg S;Helgason H;Thorleifsson G;Gudbjartsson DF;Helgason A;Magnusson OT;Thorsteinsdottir U;Stefansson K
通讯作者：
Stefansson K
DOI：
10.1073/pnas.1418652112
发表时间：
2015-03-17
影响因子：
11.1
作者：
Harris, Kelley
通讯作者：
Harris, Kelley
影响因子：
4.5
作者：
Lipson, Mark;Loh, Po-Ru;Reich, David
通讯作者：
Reich, David
影响因子：
4.5
作者：
Mathieson, Iain;Reich, David
通讯作者：
Reich, David
影响因子：
7.7
作者：
Wright, John;Small, Neil;West, Jane
通讯作者：
West, Jane