Haplotype Inference in Complex Pedigrees
Despite the desirable information contained in complex pedigree datasets, analysis methods struggle to efficiently process these datasets. The attractiveness of pedigree data sets is their power for detecting rare variants, particularly in comparison with studies of unrelated individuals. In addition, rather than assuming individuals in a study are unrelated, knowledge of their relationships can avoid spurious results due to confounding population structure effects. However, a major challenge for the applicability of pedigree methods is the ability handle complex pedigrees, having multiple founding lineages, inbreeding, and half-sibling relationships.
A key ingredient in association studies is imputation and inference of haplotypes from genotype data. Existing haplotype inference methods either do not efficiently scales to complex pedigrees or their accuracy is limited. In this paper, we present algorithms for efficient haplotype inference and imputation in complex pedigrees. Our method, PhyloPed, leverages the perfect phylogeny model, resulting in an efficient method with high accuracy. In addition, PhyloPed effectively combines the founder haplotype information from different lineages and is immune to inaccuracies in prior information about the founders.
KeywordsRecombination Rate Haplotype Inference Founder Haplotype Complex Pedigree Perfect Phylogeny
Unable to display preview. Download preview PDF.
- 2.Barrett, J.C., Hansoul, S., Nicolae, D.L., Cho, J.H., Duerr, R.H., Rioux, J.D., Brant, S.R., Silverberg, M.S., Taylor, K.D., Barmada, M.M., et al.: Genome-wide association defines more than 30 distinct susceptibility loci for crohn’s disease. Nature Genetics 40, 955–962 (2008)CrossRefPubMedPubMedCentralGoogle Scholar
- 11.Gusfield. Haplotyping as perfect phylogeny: Conceptual framework and efficient solutions. In: Proceedings of the 6th Annual International Conference on (Research in) Computational (Molecular) Biology (2002)Google Scholar
- 13.Jensen, C.S., Kong, A.: Blocking gibbs sampling for linkage analysis in large pedigrees with many loops. American Journal of Human Genetics 65 (1999)Google Scholar
- 17.Sutter, N.B., Bustamante, C.D., Chase, K., Gray, M.M., Zhao, K., Zhu, L., Padhukasahasram, B., Karlins, E., Davis, S., Jones, P.G., Quignon, P., Johnson, G.S., Parker, H.G., Fretwell, N., Mosher, D.S., Lawler, D.F., Satyaraj, E., Nordborg, M., Lark, K.G., Wayne, R.K., Ostrander, E.A.: A Single IGF1 Allele Is a Major Determinant of Small Size in Dogs. Science 316(5821), 112–115 (2007)CrossRefPubMedPubMedCentralGoogle Scholar