Identity-by-descent-based phasing and imputation in founder populations using graphical models

✍ Scribed by Kimmo Palin; Harry Campbell; Alan F. Wright; James F. Wilson; Richard Durbin

• Book ID: 102226773
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 149 KB
• Volume: 35
• Category: Article
• ISSN: 0741-0395
• DOI: 10.1002/gepi.20635

✦ Synopsis

Accurate knowledge of haplotypes, the combination of alleles co-residing on a single copy of a chromosome, enables powerful gene mapping and sequence imputation methods. Since humans are diploid, haplotypes must be derived from genotypes by a phasing process. In this study, we present a new computational model for haplotype phasing based on pairwise sharing of haplotypes inferred to be Identical-By-Descent (IBD). We apply the Bayesian network based model in a new phasing algorithm, called systematic long-range phasing (SLRP), that can capitalize on the close genetic relationships in isolated founder populations, and show with simulated and real genome-wide genotype data that SLRP substantially reduces the rate of phasing errors compared to previous phasing algorithms. Furthermore, the method accurately identifies regions of IBD, enabling linkage-like studies without pedigrees, and can be used to impute most genotypes with very low error rate. Genet. Epidemiol. 2011. © 2011 Wiley Periodicals, Inc.35:853-860, 2011