A novel tool for individual haplotype inference using mixed data

We propose a general and simple methodology using a mixture of weighted multinomial (MIXMUL) approach that combines separate haplotype information from unrelated individuals and independent trios for haplotype inference to the individual level.The new MIXMUL procedure improves over existing methods in that it can accurately estimate haplotype frequencies from mixed data sets and output probable haplotype pairs in optimized reconstruction outcomes for all subjects that have contributed to estimation. Simulation results showed that this new MIXMUL procedure competes well with the EM-based method, i.e. FAMHAP, under a few assumed scenarios.The results showed that MIXMUL can provide accurate estimates similar to those haplotype frequencies obtained from FAMHAP and output the probable haplotype pairs in the most optimal reconstruction outcome for all subjects that have contributed to estimation. If available data consist of combinations of unrelated individuals and independent trios, the MIXMUL procedure can be used to estimate the haplotype frequencies accurately and output the most likely reconstructed haplotype pairs of each subject in the estimation.Since the completion of the International HapMap Project, millions of single nucleotide polymorphisms (SNPs) and haplotype information have been deposited into public databases for studies in the fields of population genetics, evolutionary genetics, and complex disease gene mapping. Several studies have demonstrated that haplotypes can provide more power than single markers in detecting associations [1]. However, haplotype information cannot usually be obtained directly from unphased genotype data. It is possible to determine haplotypes using molecular experimental techniques, but such approaches are still expensive and labor intensive. Therefore, haplotype determination from genotype data by statistical methods is used if the estimation is done accurately.The population-based case-control design is a commonly used design