Evolution and functional impact of rare coding variation from deep sequencing of human exomes.
Evolution and functional impact of rare coding variation from deep sequencing of human exomes.
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DOI：
10.1126/science.1219240
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发表时间：
2012-07-06
期刊：
影响因子：
--
通讯作者：
NHLBI Exome Sequencing Project
中科院分区：
文献类型：
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作者：
Tennessen JA;Bigham AW;O'Connor TD;Fu W;Kenny EE;Gravel S;McGee S;Do R;Liu X;Jun G;Kang HM;Jordan D;Leal SM;Gabriel S;Rieder MJ;Abecasis G;Altshuler D;Nickerson DA;Boerwinkle E;Sunyaev S;Bustamante CD;Bamshad MJ;Akey JM;Broad GO;Seattle GO;NHLBI Exome Sequencing Project
作为了解罕见变异如何导致复杂疾病风险的第一步，我们对15585个人类蛋白质编码基因进行了测序，测序结果显示，在2440名欧洲人(n=1351)和非洲人(n=1088)祖先中，人类蛋白质编码基因的平均深度为111×。我们鉴定了超过500,000个单核苷酸变异(SNV)，其中大多数是罕见的(86%的微小等位基因频率低于0.5%)，以前未知的(82%)，以及群体特异性的(82%)。平均而言，在每个人携带的13,595个SNV中，有2.3%被预测会影响每个基因组中∼313基因的蛋白质功能，而被预测为功能重要的∼95.7%的SNV是罕见的。这种稀有功能变异的过剩是由于爆炸性的、最近的人口加速增长和弱的净化选择的综合影响。此外，我们还表明，要将罕见的变异与复杂的特征联系起来，需要大量的样本。
As a first step toward understanding how rare variants contribute to risk for complex diseases, we sequenced 15,585 human protein-coding genes to an average median depth of 111× in 2440 individuals of European (n = 1351) and African (n = 1088) ancestry. We identified over 500,000 single-nucleotide variants (SNVs), the majority of which were rare (86% with a minor allele frequency less than 0.5%), previously unknown (82%), and population-specific (82%). On average, 2.3% of the 13,595 SNVs each person carried were predicted to affect protein function of ∼313 genes per genome, and ∼95.7% of SNVs predicted to be functionally important were rare. This excess of rare functional variants is due to the combined effects of explosive, recent accelerated population growth and weak purifying selection. Furthermore, we show that large sample sizes will be required to associate rare variants with complex traits.
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影响因子：
9.8
作者：
Akey JM;Eberle MA;Rieder MJ;Carlson CS;Shriver MD;Nickerson DA;Kruglyak L
通讯作者：
Kruglyak L
影响因子：
30.8
作者：
通讯作者：
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影响因子：
4.5
作者：
Sobreira NL;Cirulli ET;Avramopoulos D;Wohler E;Oswald GL;Stevens EL;Ge D;Shianna KV;Smith JP;Maia JM;Gumbs CE;Pevsner J;Thomas G;Valle D;Hoover-Fong JE;Goldstein DB
通讯作者：
Goldstein DB
影响因子：
64.8
作者：
Frazer, Kelly A.;Ballinger, Dennis G.;Cox, David R.;Hinds, David A.;Stuve, Laura L.;Gibbs, Richard A.;Belmont, John W.;Boudreau, Andrew;Hardenbol, Paul;Leal, Suzanne M.;Pasternak, Shiran;Wheeler, David A.;Willis, Thomas D.;Yu, Fuli;Yang, Huanming;Zeng, Changqing;Gao, Yang;Hu, Haoran;Hu, Weitao;Li, Chaohua;Lin, Wei;Liu, Siqi;Pan, Hao;Tang, Xiaoli;Wang, Jian;Wang, Wei;Yu, Jun;Zhang, Bo;Zhang, Qingrun;Zhao, Hongbin;Zhao, Hui;Zhou, Jun;Gabriel, Stacey B.;Barry, Rachel;Blumenstiel, Brendan;Camargo, Amy;Defelice, Matthew;Faggart, Maura;Goyette, Mary;Gupta, Supriya;Moore, Jamie;Nguyen, Huy;Onofrio, Robert C.;Parkin, Melissa;Roy, Jessica;Stahl, Erich;Winchester, Ellen;Ziaugra, Liuda;Altshuler, David;Shen, Yan;Yao, Zhijian;Huang, Wei;Chu, Xun;He, Yungang;Jin, Li;Liu, Yangfan;Shen, Yayun;Sun, Weiwei;Wang, Haifeng;Wang, Yi;Wang, Ying;Xiong, Xiaoyan;Xu, Liang;Waye, Mary M. Y.;Tsui, Stephen K. W.;Wong, J. Tze-Fei;Galver, Luana M.;Fan, Jian-Bing;Gunderson, Kevin;Murray, Sarah S.;Oliphant, Arnold R.;Chee, Mark S.;Montpetit, Alexandre;Chagnon, Fanny;Ferretti, Vincent;Leboeuf, Martin;Olivier, Jean-Franccois;Phillips, Michael S.;Roumy, Stephanie;Sallee, Clementine;Verner, Andrei;Hudson, Thomas J.;Kwok, Pui-Yan;Cai, Dongmei;Koboldt, Daniel C.;Miller, Raymond D.;Pawlikowska, Ludmila;Taillon-Miller, Patricia;Xiao, Ming;Tsui, Lap-Chee;Mak, William;Song, You Qiang;Tam, Paul K. H.;Nakamura, Yusuke;Kawaguchi, Takahisa;Kitamoto, Takuya;Morizono, Takashi;Nagashima, Atsushi;Ohnishi, Yozo;Sekine, Akihiro;Tanaka, Toshihiro;Tsunoda, Tatsuhiko;Deloukas, Panos;Bird, Christine P.;Delgado, Marcos;Dermitzakis, Emmanouil T.;Gwilliam, Rhian;Hunt, Sarah;Morrison, Jonathan;Powell, Don;Stranger, Barbara E.;Whittaker, Pamela;Bentley, David R.;Daly, Mark J.;de Bakker, Paul I. W.;Barrett, Jeff;Chretien, Yves R.;Maller, Julian;McCarroll, Steve;Patterson, Nick;Pe'er, Itsik;Price, Alkes;Purcell, Shaun;Richter, Daniel J.;Sabeti, Pardis;Saxena, Richa;Schaffner, Stephen F.;Sham, Pak C.;Varilly, Patrick;Altshuler, David;Stein, Lincoln D.;Krishnan, Lalitha;Smith, Albert Vernon;Tello-Ruiz, Marcela K.;Thorisson, Gudmundur A.;Chakravarti, Aravinda;Chen, Peter E.;Cutler, David J.;Kashuk, Carl S.;Lin, Shin;Abecasis, Goncalo R.;Guan, Weihua;Li, Yun;Munro, Heather M.;Qin, Zhaohui Steve;Thomas, Daryl J.;McVean, Gilean;Auton, Adam;Bottolo, Leonardo;Cardin, Niall;Eyheramendy, Susana;Freeman, Colin;Marchini, Jonathan;Myers, Simon;Spencer, Chris;Stephens, Matthew;Donnelly, Peter;Cardon, Lon R.;Clarke, Geraldine;Evans, David M.;Morris, Andrew P.;Weir, Bruce S.;Tsunoda, Tatsuhiko;Johnson, Todd A.;Mullikin, James C.;Sherry, Stephen T.;Feolo, Michael;Skol, Andrew
通讯作者：
Skol, Andrew
影响因子：
64.8
作者：
通讯作者：
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