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Comparison of Haplotype Inference Methods Using Genotypic Data from Unrelated Individuals

Objective: Haplotypes are gaining popularity in studies of human genetics because they contain more information than does a single gene locus. However, current high-throughput genotyping techniques cannot produce haplotype information. Several statistical methods have recently been proposed to infer haplotypes based on unphased genotypes at several loci. The accuracy, efficiency, and computational time of these methods have been under intense scrutiny. In this report, our aim was to evaluate haplotype inference methods for genotypic data from unrelated individuals. Methods: We compared the performance of three haplotype inference methods that are currently in use – HAPLOTYPER, hap, and PHASE – by applying them to a large data set from unrelated individuals with known haplotypes. We also applied these methods to coalescent-based simulation studies using both constant size and exponential growth models. The performance of these methods, along with that of the expectation-maximization algorithm, was further compared in the context of an association study. Results: While the algorithm implemented in the software PHASE was found to be the most accurate in both real and simulated data comparisons, all four methods produced good results in the association study.