The Impact of Using Related Individuals for Haplotype Reconstruction in Population Studies

Abstract

Recent studies have highlighted the dangers of using haplotypes reconstructed directly from population data for a fine-scale mapping analysis. Family data may help resolve ambiguity, yet can be costly to obtain. This study is concerned with the following question: How much family data (if any) should be used to facilitate haplotype reconstruction in a population study? We conduct a simulation study to evaluate how changes in family information can affect the accuracy of haplotype frequency estimates and phase reconstruction. To reconstruct haplotypes, we introduce an EM-based algorithm that can efficiently accommodate unrelated individuals, parent-child trios, and arbitrarily large half-sib pedigrees. Simulations are conducted for a diverse set of haplotype frequency distributions, all of which have been previously published in empirical studies. A wide variety of important results regarding the effectiveness of using pedigree data in a population study are presented in a coherent, unified framework. Insight into the different properties of the haplotype frequency distribution that can influence experimental design is provided. We show that a preliminary estimate of the haplotype frequency distribution can be valuable in large population studies with fixed resources.