Exploring signatures of positive selection in pigmentation candidate genes in populations of East Asian ancestry.
Exploring signatures of positive selection in pigmentation candidate genes in populations of East Asian ancestry.
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DOI：
10.1186/1471-2148-13-150
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发表时间：
2013-07-12
影响因子：
3.4
通讯作者：
Parra EJ
中科院分区：
文献类型：
--
作者：
Hider JL;Gittelman RM;Shah T;Edwards M;Rosenbloom A;Akey JM;Parra EJ
目前，对东亚人群正常色素沉着变异相关基因的了解非常有限。我们使用1000个基因组I期数据集对正选择的特征进行了全基因组扫描，以识别显示东亚选择性扫描的推定特征的色素沉着基因。我们应用了广泛的方法来检测选择的签名，包括：1）旨在确定现场频谱（SFS）偏离中性预期的测试（田岛的D，费和吴的H和傅和李的D* 和F*），2）测试集中于鉴定具有扩展连锁不平衡的高频单倍型（iHS和Rsb）和3）基于群体间遗传分化的测试（LSBL）。基于从25 kb窗口的全基因组分析获得的结果，我们构建了所有窗口中每个统计量的经验分布，并确定了分布中的离群值色素沉着基因。我们的测试确定了20个与色素沉着生物学相关的基因。其中，8个基因（ATRN、EDAR、KLHL 7、MITF、OCA 2、TH、TMEM 33和TRPM 1）为极端离群值（经验分布的前0.1%）至少有一个统计，和12个基因（ADAM 17，BNC 2，CTSD，DCT，EGFR，LYST，MC1R，MLPH，OPRM 1，PDIA 6，PMEL（SILV）和TYRP 1）至少在一个统计量的经验分布中处于前1%。此外，这些基因中的八个（BNC 2、EGFR、LYST、MC 1 R、OCA 2、OPRM 1、PMEL（SILV）和TYRP 1）在关联研究中与猪的性状相关。我们确定了一些假定的色素沉着基因，在东亚显示出极不寻常的遗传变异模式。这些基因中的大多数是不同测试和/或不同人群的离群值，并且已经在之前的正选择扫描中描述过，为最近的选择扫描在这些区域留下签名的假设提供了强有力的支持。然而，有必要进行关联和功能研究，以证明这些基因在正常色素变化中的意义。
Currently, there is very limited knowledge about the genes involved in normal pigmentation variation in East Asian populations. We carried out a genome-wide scan of signatures of positive selection using the 1000 Genomes Phase I dataset, in order to identify pigmentation genes showing putative signatures of selective sweeps in East Asia. We applied a broad range of methods to detect signatures of selection including: 1) Tests designed to identify deviations of the Site Frequency Spectrum (SFS) from neutral expectations (Tajima’s D, Fay and Wu’s H and Fu and Li’s D* and F*), 2) Tests focused on the identification of high-frequency haplotypes with extended linkage disequilibrium (iHS and Rsb) and 3) Tests based on genetic differentiation between populations (LSBL). Based on the results obtained from a genome wide analysis of 25 kb windows, we constructed an empirical distribution for each statistic across all windows, and identified pigmentation genes that are outliers in the distribution. Our tests identified twenty genes that are relevant for pigmentation biology. Of these, eight genes (ATRN, EDAR, KLHL7, MITF, OCA2, TH, TMEM33 and TRPM1,) were extreme outliers (top 0.1% of the empirical distribution) for at least one statistic, and twelve genes (ADAM17, BNC2, CTSD, DCT, EGFR, LYST, MC1R, MLPH, OPRM1, PDIA6, PMEL (SILV) and TYRP1) were in the top 1% of the empirical distribution for at least one statistic. Additionally, eight of these genes (BNC2, EGFR, LYST, MC1R, OCA2, OPRM1, PMEL (SILV) and TYRP1) have been associated with pigmentary traits in association studies. We identified a number of putative pigmentation genes showing extremely unusual patterns of genetic variation in East Asia. Most of these genes are outliers for different tests and/or different populations, and have already been described in previous scans for positive selection, providing strong support to the hypothesis that recent selective sweeps left a signature in these regions. However, it will be necessary to carry out association and functional studies to demonstrate the implication of these genes in normal pigmentation variation.
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来自1,092个人基因组的遗传变异的综合图。
影响因子：
64.8
作者：
通讯作者：
--
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：
3.4
作者：
Alonso S;Izagirre N;Smith-Zubiaga I;Gardeazabal J;Díaz-Ramón JL;Díaz-Pérez JL;Zelenika D;Boyano MD;Smit N;de la Rúa C
通讯作者：
de la Rúa C
影响因子：
7
作者：
Chen, Hua;Patterson, Nick;Reich, David
通讯作者：
Reich, David
影响因子：
2.9
作者：
Elias, Peter M.;Menon, Gopinathan;Wetzel, Bruce K.;Williams, John (Jack) W.
通讯作者：
Williams, John (Jack) W.