Complete genome phasing of family quartet by combination of genetic, physical and population-based phasing analysis.
Complete genome phasing of family quartet by combination of genetic, physical and population-based phasing analysis.
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通过基于遗传，物理和人群分析分析的结合，对家庭四重奏的完全基因组进行分阶段。
DOI：
10.1371/journal.pone.0064571
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bouhassira EE
中科院分区：
文献类型：
--
作者：
Lajugie J;Mukhopadhyay R;Schizas M;Lailler N;Fourel N;Bouhassira EE
定相基因组图谱对于了解遗传和表观遗传调控以及疾病机制，特别是亲本印记缺陷非常重要。定相对于评估遗传变异的功能后果以及精确定义单倍型块也至关重要，这有助于了解群体水平上的基因流和基因型-表型关联。通过分析家族四重体进行的传输定相允许对所有变异的 95% 进行定相，因为无法对一致的杂合位置进行定相。在这里，我们报告了一种基于传输分析、交错大小文库双端测序的物理定相和基于群体的分析相结合的定相方法。以 120 倍覆盖率对健康白种人四重体进行测序，并结合物理和传输定相，产生了四重体中约 99.8% 的 SNP、插入缺失和结构变异的定相基因型，定相率明显高于使用任何单定相方法所能达到的水平。使用过滤器组合获得每个基因组和每个碱基的假阳性 SNP 错误率低于 10*E-7。我们提供 SNP、插入缺失和结构变异的完整列表、单倍型块大小的分析以及假阳性和阴性变异检出错误率的分析。改进的基因组定相和家族测序将增强全基因组测序作为临床诊断工具的能力，并具有无数的基础科学应用。
Phased genome maps are important to understand genetic and epigenetic regulation and disease mechanisms, particularly parental imprinting defects. Phasing is also critical to assess the functional consequences of genetic variants, and to allow precise definition of haplotype blocks which is useful to understand gene-flow and genotype-phenotype association at the population level. Transmission phasing by analysis of a family quartet allows the phasing of 95% of all variants as the uniformly heterozygous positions cannot be phased. Here, we report a phasing method based on a combination of transmission analysis, physical phasing by pair-end sequencing of libraries of staggered sizes and population-based analysis. Sequencing of a healthy Caucasians quartet at 120x coverage and combination of physical and transmission phasing yielded the phased genotypes of about 99.8% of the SNPs, indels and structural variants present in the quartet, a phasing rate significantly higher than what can be achieved using any single phasing method. A false positive SNP error rate below 10*E-7 per genome and per base was obtained using a combination of filters. We provide a complete list of SNPs, indels and structural variants, an analysis of haplotype block sizes, and an analysis of the false positive and negative variant calling error rates. Improved genome phasing and family sequencing will increase the power of genome-wide sequencing as a clinical diagnosis tool and has myriad basic science applications.
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影响因子：
64.8
作者：
Peters, Brock A.;Kermani, Bahram G.;Sparks, Andrew B.;Alferov, Oleg;Hong, Peter;Alexeev, Andrei;Jiang, Yuan;Dahl, Fredrik;Tang, Y. Tom;Haas, Juergen;Robasky, Kimberly;Zaranek, Alexander Wait;Lee, Je-Hyuk;Ball, Madeleine Price;Peterson, Joseph E.;Perazich, Helena;Yeung, George;Liu, Jia;Chen, Linsu;Kennemer, Michael I.;Pothuraju, Kaliprasad;Konvicka, Karel;Tsoupko-Sitnikov, Mike;Pant, Krishna P.;Ebert, Jessica C.;Nilsen, Geoffrey B.;Baccash, Jonathan;Halpern, Aaron L.;Church, George M.;Drmanac, Radoje
通讯作者：
Drmanac, Radoje
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：
48
作者：
Xiao, Ming;Wan, Eunice;Chu, Catherine;Hsueh, Wen-Chi;Cao, Yang;Kwok, Pui-Yan
通讯作者：
Kwok, Pui-Yan
影响因子：
64.8
作者：
LI, HH;GYLLENSTEN, UB;ARNHEIM, N
通讯作者：
ARNHEIM, N
DOI：
10.1073/pnas.1016725108
发表时间：
2011-01-04
影响因子：
11.1
作者：
Yang, Hong;Chen, Xi;Wong, Wing Hung
通讯作者：
Wong, Wing Hung