A unified test of linkage analysis and rare-variant association for analysis of pedigree sequence data.
A unified test of linkage analysis and rare-variant association for analysis of pedigree sequence data.
复制标题
DOI：
10.1038/nbt.2895
复制
发表时间：
2014-07
影响因子：
46.9
通讯作者：
Huff, Chad D.
中科院分区：
文献类型：
--
作者：
Hu, Hao;Roach, Jared C.;Coon, Hilary;Guthery, Stephen L.;Voelkerding, Karl V.;Margraf, Rebecca L.;Durtschi, Jacob D.;Tavtigian, Sean V.;Shankaracharya;Wu, Wilfred;Scheet, Paul;Wang, Shuoguo;Xing, Jinchuan;Glusman, Gustavo;Hubley, Robert;Li, Hong;Garg, Vidu;Moore, Barry;Hood, Leroy;Galas, David J.;Srivastava, Deepak;Reese, Martin G.;Jorde, Lynn B.;Yandell, Mark;Huff, Chad D.
相关个体的高通量测序已成为研究人类疾病的重要工具。然而，由于技术复杂性和缺乏可用的工具，大多数基于家系的测序研究依赖于次优分析的临时组合。在这里，我们提出谱系- vaast (pVAAST)，一种疾病基因鉴定工具，专为高通量谱系序列数据而设计。pVAAST使用基于序列的模型进行变异和基于基因的连锁分析。然后将连锁信息与功能预测和罕见变异病例-对照关联信息结合在一个统一的统计框架中。pVAAST在模拟中优于连锁和罕见变异关联测试，并从三个具有显性、隐性和从头遗传模式的人类家系的全基因组序列数据中识别出致病基因。该方法对不完全外显率和基因座异质性具有较强的鲁棒性，适用于多种遗传性状。pVAAST在单个谱系中的单基因、高外显率表型到涉及数百个谱系的高多基因、常见表型的研究中保持高功率。
High-throughput sequencing of related individuals has become an important tool for studying human disease. However, owing to technical complexity and lack of available tools, most pedigree-based sequencing studies rely on an ad hoc combination of suboptimal analyses. Here we present pedigree-VAAST (pVAAST), a disease-gene identification tool designed for high-throughput sequence data in pedigrees. pVAAST uses a sequence-based model to perform variant and gene-based linkage analysis. Linkage information is then combined with functional prediction and rare variant case-control association information in a unified statistical framework. pVAAST outperformed linkage and rare-variant association tests in simulations and identified disease-causing genes from whole-genome sequence data in three human pedigrees with dominant, recessive and de novo inheritance patterns. The approach is robust to incomplete penetrance and locus heterogeneity and is applicable to a wide variety of genetic traits. pVAAST maintains high power across studies of monogenic, high-penetrance phenotypes in a single pedigree to highly polygenic, common phenotypes involving hundreds of pedigrees.
登录
查看更多内容
影响因子：
9.2
作者：
Domyan, Eric T.;Guernsey, Michael W.;Kronenberg, Zev;Krishnan, Shreyas;Boissy, Raymond E.;Vickrey, Anna I.;Rodgers, Clifford;Cassidy, Pamela;Leachman, Sancy A.;Fondon, John W., III;Yandell, Mark;Shapiro, Michael D.
通讯作者：
Shapiro, Michael D.
影响因子：
14.9
作者：
Dreszer TR;Karolchik D;Zweig AS;Hinrichs AS;Raney BJ;Kuhn RM;Meyer LR;Wong M;Sloan CA;Rosenbloom KR;Roe G;Rhead B;Pohl A;Malladi VS;Li CH;Learned K;Kirkup V;Hsu F;Harte RA;Guruvadoo L;Goldman M;Giardine BM;Fujita PA;Diekhans M;Cline MS;Clawson H;Barber GP;Haussler D;James Kent W
通讯作者：
James Kent W
影响因子：
30.8
作者：
Li, Yingrui;Vinckenbosch, Nicolas;Wang, Jun
通讯作者：
Wang, Jun
影响因子：
30.8
作者：
Hoischen, Alexander;van Bon, Bregje W. M.;Veltman, Joris A.
通讯作者：
Veltman, Joris A.
影响因子：
7
作者：
Boisson-Dupuis S;Kong XF;Okada S;Cypowyj S;Puel A;Abel L;Casanova JL
通讯作者：
Casanova JL