Application of homozygosity haplotype analysis to genetic mapping with high-density SNP genotype data.
Application of homozygosity haplotype analysis to genetic mapping with high-density SNP genotype data.
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DOI：
10.1371/journal.pone.0005280
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Dubé MP
中科院分区：
文献类型：
--
作者：
Jiang H;Orr A;Guernsey DL;Robitaille J;Asselin G;Samuels ME;Dubé MP
在具有单一疾病基因引入的单基因遗传性疾病分离的家族中，患者与血统认同（IBD）共享携带突变的染色体间隔。通常通过使用微卫星或SNP基因型数据的多点连锁和定相单体型分析来检测和定义围绕实际致病突变的这种共享染色体间隔或单体型。高密度SNP基因型数据对传统遗传分析提出了计算挑战。最近提出了一种新的非参数方法，称为纯合性单倍型（HH），用于使用高密度SNP基因型数据在全基因组范围内搜索患者之间共享的常染色体片段。HH的适用性和有效性，在确定潜在的连锁致病基因与高密度SNP基因型数据进行了研究与一系列的单基因疾病在加拿大东部人群中确定。HH的方法进行了验证，使用基因型的患者从一个家庭的影响与罕见的常染色体显性遗传病施奈德结晶角膜营养不良。HH仅使用4名受影响受试者的基因型准确检测到包含致病基因UBIAD 1的101 Mb基因组间隔。成功应用HH来确定一个中心周围视网膜疾病家族的潜在联系，表明HH可以应用于进行基于家族的关联分析，将受影响和未受影响的家族成员分别作为病例和对照。提出了一种全基因组筛选HH已知致病基因或基因座的新策略，如肌阵挛肌张力障碍和肾衰竭队列的应用所示。我们对HH方法的研究表明，HH在识别潜在疾病相关区域方面非常有效。HH有望成为一种有效的替代测序或基于微卫星的精细定位方法，用于遗传病研究中已知致病基因的筛选。
In families segregating a monogenic genetic disorder with a single disease gene introduction, patients share a mutation-carrying chromosomal interval with identity-by-descent (IBD). Such a shared chromosomal interval or haplotype, surrounding the actual pathogenic mutation, is typically detected and defined by multipoint linkage and phased haplotype analysis using microsatellite or SNP genotype data. High-density SNP genotype data presents a computational challenge for conventional genetic analyses. A novel non-parametric method termed Homozygosity Haplotype (HH) was recently proposed for the genome-wide search of the autosomal segments shared among patients using high density SNP genotype data. The applicability and the effectiveness of HH in identifying the potential linkage of disease causative gene with high-density SNP genotype data were studied with a series of monogenic disorders ascertained in eastern Canadian populations. The HH approach was validated using the genotypes of patients from a family affected with a rare autosomal dominant disease Schnyder crystalline corneal dystrophy. HH accurately detected the ∼1 Mb genomic interval encompassing the causative gene UBIAD1 using the genotypes of only four affected subjects. The successful application of HH to identify the potential linkage for a family with pericentral retinal disorder indicates that HH can be applied to perform family-based association analysis by treating affected and unaffected family members as cases and controls respectively. A new strategy for the genome-wide screening of known causative genes or loci with HH was proposed, as shown the applications to a myoclonus dystonia and a renal failure cohort. Our study of the HH approach demonstrates that HH is very efficient and effective in identifying potential disease linked region. HH has the potential to be used as an efficient alternative approach to sequencing or microsatellite-based fine mapping for screening the known causative genes in genetic disease study.
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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：
5.8
作者：
Halperin, E;Eskin, E
通讯作者：
Eskin, E
影响因子：
1.8
作者：
Geller, F;Ziegler, A
通讯作者：
Ziegler, A
影响因子：
1.7
作者：
Gusfield, D
通讯作者：
Gusfield, D
影响因子：
9.8
作者：
Lunetta, KL;Faraone, SV;Laird, NM
通讯作者：
Laird, NM