Deep resequencing reveals excess rare recent variants consistent with explosive population growth.
Deep resequencing reveals excess rare recent variants consistent with explosive population growth.
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DOI：
10.1038/ncomms1130
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发表时间：
2010-11-30
影响因子：
16.6
通讯作者：
Sing, Charles F.
中科院分区：
文献类型：
--
作者：
Coventry, Alex;Bull-Otterson, Lara M.;Liu, Xiaoming;Clark, Andrew G.;Maxwell, Taylor J.;Crosby, Jacy;Hixson, James E.;Rea, Thomas J.;Muzny, Donna M.;Lewis, Lora R.;Wheeler, David A.;Sabo, Aniko;Lusk, Christine;Weiss, Kenneth G.;Akbar, Humeira;Cree, Andrew;Hawes, Alicia C.;Newsham, Irene;Varghese, Robin T.;Villasana, Donna;Gross, Shannon;Joshi, Vandita;Santibanez, Jireh;Morgan, Margaret;Chang, Kyle;Hale, Walker;Templeton, Alan R.;Boerwinkle, Eric;Gibbs, Richard;Sing, Charles F.
准确确定罕见变异的分布是人类遗传学的一个重要目标，但迄今为止，对足够大的样本进行重新测序仍不可行。在这里，我们应用基因组 PCR 扩增子的桑格测序对 13,715 人（10,422 名欧洲裔美国人和 3,293 名非洲裔美国人）的糖尿病相关基因 KCNJ11 和 HHEX 进行了重新测序，并使用 454 焦磷酸测序验证了可能含有罕见变异的扩增子。我们观察到的变异（预期变异位点计数~578）比根据早期调查预测的要多得多，早期调查只能捕获常见变异的分布。与早期基于常见变异的估计相比，我们的模型显示出人口加速增长的明显遗传信号，这表明人类拥有无数罕见的有害变异，当代人群的疾病风险和疾病负担可能会受到罕见变异分布的严重影响。 为了全面记录人类罕见的遗传变异，需要检查许多样本。在这项研究中，考文垂等人。对 13,715 名人类的两个基因 KCNJ11 和 HHEX 进行了重新测序，得出的结论是，大多数序列变异是最近出现的，而且变异程度比预期的要大。
Accurately determining the distribution of rare variants is an important goal of human genetics, but resequencing of a sample large enough for this purpose has been unfeasible until now. Here, we applied Sanger sequencing of genomic PCR amplicons to resequence the diabetes-associated genes KCNJ11 and HHEX in 13,715 people (10,422 European Americans and 3,293 African Americans) and validated amplicons potentially harbouring rare variants using 454 pyrosequencing. We observed far more variation (expected variant-site count ∼578) than would have been predicted on the basis of earlier surveys, which could only capture the distribution of common variants. By comparison with earlier estimates based on common variants, our model shows a clear genetic signal of accelerating population growth, suggesting that humanity harbours a myriad of rare, deleterious variants, and that disease risk and the burden of disease in contemporary populations may be heavily influenced by the distribution of rare variants. To fully catalogue rare genetic variation in humans, many samples need to be examined. In this study, Coventry et al. resequenced two genes, KCNJ11 and HHEX, in 13,715 humans, and concluded that most of the sequence variation arose recently and that variation is greater than expected.
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影响因子：
4.5
作者：
Gutenkunst RN;Hernandez RD;Williamson SH;Bustamante CD
通讯作者：
Bustamante CD
DOI：
10.1073/pnas.0906182107
发表时间：
2010-01-26
影响因子：
11.1
作者：
Eyre-Walker, Adam
通讯作者：
Eyre-Walker, Adam
影响因子：
14.9
作者：
Ramensky, V;Bork, P;Sunyaev, S
通讯作者：
Sunyaev, S
影响因子：
30.8
作者：
通讯作者：
--
影响因子：
14.9
作者：
Nickerson, DA;Tobe, VO;Taylor, SL
通讯作者：
Taylor, SL