The characterization of twenty sequenced human genomes.
The characterization of twenty sequenced human genomes.
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DOI：
10.1371/journal.pgen.1001111
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发表时间：
2010-09-09
期刊：
影响因子：
4.5
通讯作者：
Goldstein DB
中科院分区：
文献类型：
--
作者：
Pelak K;Shianna KV;Ge D;Maia JM;Zhu M;Smith JP;Cirulli ET;Fellay J;Dickson SP;Gumbs CE;Heinzen EL;Need AC;Ruzzo EK;Singh A;Campbell CR;Hong LK;Lornsen KA;McKenzie AM;Sobreira NL;Hoover-Fong JE;Milner JD;Ottman R;Haynes BF;Goedert JJ;Goldstein DB
我们提出了20个人类基因组的分析，以评估识别罕见的功能性变异，有助于感兴趣的表型的前景。我们在高覆盖率下对10个严重血友病A患者的“病例”基因组和10个“对照”基因组进行了测序。我们总结了从这种规模的研究中出现的遗传变异的数量，并通过确认血友病A的原因在该数据集中很容易识别，为鉴定罕见和高度渗透的功能变异提供了概念证明。我们还表明，在前15个个体被测序后，每个基因组发现的新单核苷酸变异（SNV）的数量似乎稳定在每个基因组约144，000个新变异。最后，我们发现，平均而言，每个基因组携带165个纯合蛋白质截短或停止损失的基因变异代表了一组不同的途径。我们在这里报告了20个不同个体的几乎完整的基因组序列，使用“下一代”测序技术确定。我们使用这些数据来表征这种大小的样本中人类携带的遗传变异类型，据我们所知，这是已报道的最大的一组无关基因组序列。我们总结了每个基因组中不同类别的变异，并在所有20个基因组中进行了总结，发现了数量惊人的变异，这些变异预计会减少或去除许多不同基因编码的蛋白质。这项工作提供了有关人类遗传变异范围的重要基础信息，并提出了进一步探索这些遗传变异与人类疾病之间关系的方法。
We present the analysis of twenty human genomes to evaluate the prospects for identifying rare functional variants that contribute to a phenotype of interest. We sequenced at high coverage ten “case” genomes from individuals with severe hemophilia A and ten “control” genomes. We summarize the number of genetic variants emerging from a study of this magnitude, and provide a proof of concept for the identification of rare and highly-penetrant functional variants by confirming that the cause of hemophilia A is easily recognizable in this data set. We also show that the number of novel single nucleotide variants (SNVs) discovered per genome seems to stabilize at about 144,000 new variants per genome, after the first 15 individuals have been sequenced. Finally, we find that, on average, each genome carries 165 homozygous protein-truncating or stop loss variants in genes representing a diverse set of pathways. We report here the nearly complete genomic sequence of 20 different individuals, determined using “next-generation” sequencing technologies. We use these data to characterize the type of genetic variation carried by humans in a sample of this size, which is to our knowledge the largest set of unrelated genomic sequences that have been reported. We summarize different categories of variation in each genome, and in total across all 20 of the genomes, finding a surprising number of variants predicted to reduce or remove the proteins encoded by many different genes. This work provides important fundamental information about the scope of human genetic variation, and suggests ways to further explore the relationship between these genetic variants and human disease.
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影响因子：
30.8
作者：
Alkan, Can;Kidd, Jeffrey M.;Marques-Bonet, Tomas;Aksay, Gozde;Antonacci, Francesca;Hormozdiari, Fereydoun;Kitzman, Jacob O.;Baker, Carl;Malig, Maika;Mutlu, Onur;Sahinalp, S. Cenk;Gibbs, Richard A.;Eichler, Evan E.
通讯作者：
Eichler, Evan E.
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：
30.8
作者：
Iafrate, AJ;Feuk, L;Lee, C
通讯作者：
Lee, C
影响因子：
5.8
作者：
Malhis, Nawar;Jones, Steven J. M.
通讯作者：
Jones, Steven J. M.
影响因子：
4.4
作者：
Hale MC;McCormick CR;Jackson JR;Dewoody JA
通讯作者：
Dewoody JA