University of Washington - Department of Statistics
Allele-sharing methods provide a robust approach to linkage detection for complex traits using pedigree data. Affected related individuals have increased probability of sharing genes identical-by-descent (IBD) at trait loci and hence also at linked marker loci at which they therefore show increased similarity over that predicted under Mendelian segregation. Relatives of discordant phenotype have decreased probability of sharing genes IBD at trait loci and hence have decreased similarity at linked markers.
These methods are well developed for affected sib pairs or small nuclear families or moderate size pedigrees. The applicability of different steps involved in existing allele-sharing methods can be questioned if applied on extended pedigrees. We have proposed different approaches for efficient implementation of allele-sharing methods on extended pedigrees. I will present a new likelihood-based approach that models the segregation of alleles at a location conditional on the affectation status of individuals in a pedigree without making any assumption about the underlying trait model. I will discuss different properties of the new model. The distribution of the likelihood-ratio statistic both in presence of complete and of incomplete IBD information in pedigrees will be discussed. The performance of the model in detecting linkage will be illustrated with different examples.