Mosaic Haplotype Reference Panels for Minority Populations

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We aim to establish the haplotype reference panels for haplotype phasing in the US minority populations. Haplotype refers to a group of alleles inherited on a single chromosome; it describes the cis-conformation among alleles at different polymorphic loci and is thus essential for deciphering the synergistic cis-interactions among multiple variants. Haplotypes may play crucial roles in diverse contexts, including linkage analysis, association studies, population genetics, medical genetics and pharmacogenetics. As humans are diploid organisms, genetic information will be incomplete without the haplotypes ultimately. Recently a large reference panel has been established for European-derived populations (HRC, The Haplotype Reference Consortium), and the first release consists of 64,976 haplotypes from 20 large cohorts. However, there is a void of haplotype reference panel for the minority populations. First, minority populations are underrepresented in genome studies and thus the haplotypes are not available for many African Subpopulations. Second, both African-Americans and Latinos are heavily admixed populations, which have shaped their genomes into mosaic genomes. In these mosaic genomes, different genomic regions within the same individual were inherited from ancestors of different ethnic backgrounds, so any single-ethnicity reference panel cannot cover well the ancestral origins for an admixed individual for haplotype phasing. Third, due to dramatic variations from individuals to individuals on the admixture recipe and ratio, the phasing algorithms based on haplotype frequencies that have been used on homogeneous populations may not work well on heterogeneous populations such as African-Americans and Latinos. In this proposal, we will explore potential solutions for these challenges. Specifically, we will strategically utilize the large volume of existing unphased genotype datasets and convert them into haplotype references for minority populations; we will implement this reference panel and a haplotype phasing software into a web server, and incorporate a component of local ancestry determination with the aMAP software into the application package. The goal is to fill this void by solving this haplotype reference issue in minority populations.