domingo, 8 de junio de 2014

A unified test of linkage analysis and rare-v... [Nat Biotechnol. 2014] - PubMed - NCBI

A unified test of linkage analysis and rare-v... [Nat Biotechnol. 2014] - PubMed - NCBI

 2014 May 18. doi: 10.1038/nbt.2895. [Epub ahead of print]

A unified test of linkage analysis and rare-variant association for analysis of pedigree sequence data.


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.

[PubMed - as supplied by publisher]

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