title: 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.
authors.affiliation: School of Informatics, University of Edinburgh, Edinburgh EH1 2QL, United Kingdom. s0197809@sms.ed.ac.uk
authors.forename: Michael T
authors.initials: MT
authors.lastname: Schouten
authors.forename: Christopher K I
authors.initials: CK
authors.lastname: Williams
authors.forename: Chris S
authors.initials: CS
authors.lastname: Haley
mesh_terms: D000465:Algorithms; D000818:Animals; D016022:Case-Control Studies; D003198:Computer Simulation; D005260:Female; D005787:Gene Frequency; D005828:Genetics, Population; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008957:Models, Genetic