Analysis of protein-coding genetic variation in 60,706 humans.
Analysis of protein-coding genetic variation in 60,706 humans.
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分析60,706人的蛋白质编码遗传变异。
DOI：
10.1038/nature19057
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发表时间：
2016-08-18
期刊：
影响因子：
64.8
通讯作者：
MacArthur, Daniel G.
中科院分区：
文献类型：
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作者：
Lek, Monkol;Karczewski, Konrad J.;Minikel, Eric V.;Samocha, Kaitlin E.;Banks, Eric;Fennell, Timothy;O'Donnell-Luria, Anne H.;Ware, James S.;Hill, Andrew J.;Cummings, Beryl B.;Tukiainen, Taru;Birnbaum, Daniel P.;Kosmicki, Jack A.;Duncan, Laramie E.;Estrada, Karol;Zhao, Fengmei;Zou, James;Pierce-Hollman, Emma;Berghout, Joanne;Cooper, David N.;Deflaux, Nicole;DePristo, Mark;Do, Ron;Flannick, Jason;Fromer, Menachem;Gauthier, Laura;Goldstein, Jackie;Gupta, Namrata;Howrigan, Daniel;Kiezun, Adam;Kurki, Mitja I.;Moonshine, Ami Levy;Natarajan, Pradeep;Orozeo, Lorena;Peloso, Gina M.;Poplin, Ryan;Rivas, Manuel A.;Ruano-Rubio, Valentin;Rose, Samuel A.;Ruderfer, Douglas M.;Shakir, Khalid;Stenson, Peter D.;Stevens, Christine;Thomas, Brett P.;Tiao, Grace;Tusie-Luna, Maria T.;Weisburd, Ben;Won, Hong-Hee;Yu, Dongmei;Altshuler, David M.;Ardissino, Diego;Boehnke, Michael;Danesh, John;Donnelly, Stacey;Elosua, Roberto;Florez, Jose C.;Gabriel, Stacey B.;Getz, Gad;Glatt, Stephen J.;Hultman, Christina M.;Kathiresan, Sekar;Laakso, Markku;NcCarroll, Steven;McCarthy, Mark I.;McGovern, Dermot;McPherson, Ruth;Neale, Benjamin M.;Palotie, Aarno;Purcell, Shaun M.;Saleheen, Danish;Scharf, Jeremiah M.;Sklar, Pamela;Sullivan, Patrick F.;Tuomilehto, Jaakko;Tsuang, Ming T.;Watkins, Hugh C.;Wilson, James G.;Daly, Mark J.;MacArthur, Daniel G.
人类遗传变异的大规模参考数据集对于DNA序列变化的医学和功能解释至关重要。我们描述了作为外显子组聚合联盟（ExAC）的一部分生成的60，706个不同种族个体的高质量外显子组（蛋白质编码区）序列数据的聚合和分析。这个人类遗传多样性的目录平均每八个外显子组碱基就有一个变异，为广泛的突变复发的存在提供了直接证据。我们已经使用该目录来计算序列变异的致病性的客观指标，并识别出针对各种突变类别进行强选择的基因;识别出3，230个截短变异几乎完全耗尽的基因，其中72%目前没有确定的人类疾病表型。最后，我们证明了这些数据可以用于有效地过滤候选致病变异，并用于发现人类蛋白质编码基因中的“敲除”变异。
Large-scale reference data sets of human genetic variation are critical for the medical and functional interpretation of DNA sequence changes. We describe the aggregation and analysis of high-quality exome (protein-coding region) sequence data for 60,706 individuals of diverse ethnicities generated as part of the Exome Aggregation Consortium (ExAC). This catalogue of human genetic diversity contains an average of one variant every eight bases of the exome, and provides direct evidence for the presence of widespread mutational recurrence. We have used this catalogue to calculate objective metrics of pathogenicity for sequence variants, and to identify genes subject to strong selection against various classes of mutation; identifying 3,230 genes with near-complete depletion of truncating variants with 72% having no currently established human disease phenotype. Finally, we demonstrate that these data can be used for the efficient filtering of candidate disease-causing variants, and for the discovery of human “knockout” variants in protein-coding genes.
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DOI：
10.1126/science.1215040
发表时间：
2012-02-17
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
MacArthur DG;Balasubramanian S;Frankish A;Huang N;Morris J;Walter K;Jostins L;Habegger L;Pickrell JK;Montgomery SB;Albers CA;Zhang ZD;Conrad DF;Lunter G;Zheng H;Ayub Q;DePristo MA;Banks E;Hu M;Handsaker RE;Rosenfeld JA;Fromer M;Jin M;Mu XJ;Khurana E;Ye K;Kay M;Saunders GI;Suner MM;Hunt T;Barnes IH;Amid C;Carvalho-Silva DR;Bignell AH;Snow C;Yngvadottir B;Bumpstead S;Cooper DN;Xue Y;Romero IG;1000 Genomes Project Consortium;Wang J;Li Y;Gibbs RA;McCarroll SA;Dermitzakis ET;Pritchard JK;Barrett JC;Harrow J;Hurles ME;Gerstein MB;Tyler-Smith C
通讯作者：
Tyler-Smith C
影响因子：
4.5
作者：
Dewey FE;Grove ME;Priest JR;Waggott D;Batra P;Miller CL;Wheeler M;Zia A;Pan C;Karzcewski KJ;Miyake C;Whirl-Carrillo M;Klein TE;Datta S;Altman RB;Snyder M;Quertermous T;Ashley EA
通讯作者：
Ashley EA
影响因子：
64.8
作者：
Li, Heng;Durbin, Richard
通讯作者：
Durbin, Richard
影响因子：
9.8
作者：
Piton, Amelie;Redin, Claire;Mandel, Jean-Louis
通讯作者：
Mandel, Jean-Louis
影响因子：
64.8
作者：
Jeong, H;Mason, SP;Oltvai, ZN
通讯作者：
Oltvai, ZN