Evaluation of haplotype inference using definitive haplotype data obtained from complete hydatidiform moles, and its significance for the analyses of positively selected regions.
Evaluation of haplotype inference using definitive haplotype data obtained from complete hydatidiform moles, and its significance for the analyses of positively selected regions.
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使用从完整的氢摩尔痣获得的确定性单倍型数据评估单倍型推断，及其在分析积极选择区域的重要性。
DOI：
10.1371/journal.pgen.1000468
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发表时间：
2009-05
期刊：
影响因子：
4.5
通讯作者：
Hayashi K
中科院分区：
文献类型：
--
作者：
Higasa K;Kukita Y;Kato K;Wake N;Tahira T;Hayashi K
HapMap计划构建的单倍型图谱是疾病基因、群体结构和进化的遗传学研究中的宝贵资源。在该项目中，高加索人和非洲人的单倍型是相当准确的推断，主要是基于孟德尔遗传规则使用的基因型的三。然而，亚洲单倍型是基于群体遗传学从无关个体的基因型推断的，并且不太准确。因此，需要评估这种不准确性对下游分析的影响。我们确定了真正的日本单倍型的基因分型100个完整的葡萄胎（CHM），每个携带一个基因组来自一个精子，使用Affytek 500 K阵列。然后，我们评估了推断的单倍型如何与真实的单倍型不同，通过使用程序PHASE，fastPHASE和Beagle对伪个体化的真实单倍型进行定相。我们发现，在不同的基因组区域，特别是MHC基因座，扩展的单倍型纯合性（EHH），这是一个积极的选择措施，是模糊的扩展时，推断亚洲单倍型数据被用来检测。然后，我们使用新的统计量XDiHH绘制了基因组，该统计量直接检测真实和推断的单倍型之间的差异，以确定EHH扩增。我们还表明，这里提出的真实单倍型数据是有用的，以评估和提高亚洲基因型定相的准确性。精确的单倍型图谱是进行各种遗传研究的首选，包括鉴定疾病相关基因座和解剖进化机制，如选择和重组。对于二倍体生物，当我们使用广泛使用的高通量技术获得信息时，单倍型信息以基因型的形式出现。从基因型中提取单倍型信息的过程称为定相，如果基因型来自相关个体，例如亲子三人组，则可以通过考虑孟德尔遗传规则所施加的约束来准确完成。对于没有家族信息的基因型数据，通过基于单倍型聚类的方法之一进行定相，并且已知推断的单倍型不太准确。在这里，我们通过实验确定了全基因组的确定性单倍型，使用日本完整的葡萄胎（CHM），其中每一个都携带来自一个精子的基因组。使用这些资源，我们问，如果确定的单倍型数据可以检测到长距离的信息，已被掩盖时，我们只依赖于单倍型推断聚类。我们还表明，通过引入确定的单倍型作为参考，推断无关个体的单倍型显着改善。
The haplotype map constructed by the HapMap Project is a valuable resource in the genetic studies of disease genes, population structure, and evolution. In the Project, Caucasian and African haplotypes are fairly accurately inferred, based mainly on the rules of Mendelian inheritance using the genotypes of trios. However, the Asian haplotypes are inferred from the genotypes of unrelated individuals based on population genetics, and are less accurate. Thus, the effects of this inaccuracy on downstream analyses needs to be assessed. We determined true Japanese haplotypes by genotyping 100 complete hydatidiform moles (CHM), each carrying a genome derived from a single sperm, using Affymetrix 500 K Arrays. We then assessed how inferred haplotypes can differ from true haplotypes, by phasing pseudo-individualized true haplotypes using the programs PHASE, fastPHASE, and Beagle. We found that, at various genomic regions, especially the MHC locus, the expansion of extended haplotype homozygosity (EHH), which is a measure of positive selection, is obscured when inferred Asian haplotype data is used to detect the expansion. We then mapped the genome using a new statistic, XDiHH, which directly detects the difference between the true and inferred haplotypes, in the determination of EHH expansion. We also show that the true haplotype data presented here is useful to assess and improve the accuracy of phasing of Asian genotypes. Precise haplotype maps are preferred for the performance of a variety of genetic studies including identification of disease-associated loci and dissection of evolutionary mechanisms such as selection and recombination. For diploid organisms, the haplotype information appears as the genotypes when we obtain the information using widely used high-throughput techniques. The process of extracting haplotype information from genotypes is called phasing, which can be accurately done if the genotypes are from related individuals, such as parent–child trios, by considering the constraints imposed by the rules of Mendelian inheritance. For the genotype data without family information, phasing is done by one of the methods that are based on haplotype clustering, and the inferred haplotypes are known to be less accurate. Here, we experimentally determined genome-wide definitive haplotypes using a collection of Japanese complete hydatidiform moles (CHM), each of which carries a genome derived from a single sperm. Using these resources, we asked if the definitive haplotype data can detect long-distance information that has been obscured when we rely solely on the haplotypes inferred by clustering. We also show that by introducing definitive haplotypes as references, inference of haplotypes of unrelated individuals is significantly improved.
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影响因子：
30.8
作者：
Marchini, Jonathan;Howie, Bryan;Donnelly, Peter
通讯作者：
Donnelly, Peter
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：
56.9
作者：
McVean, GAT;Myers, SR;Donnelly, P
通讯作者：
Donnelly, P
影响因子：
9.8
作者：
Bersaglieri, T;Sabeti, PC;Hirschhorn, JN
通讯作者：
Hirschhorn, JN
影响因子：
2.1
作者：
Andres, Aida M.;Clark, Andrew G.;Hixson, James E.
通讯作者：
Hixson, James E.