Knowledge of chromosome-length haplotypes will not only advance our understanding of the relationship between DNA and phenotypes, but will also promote a variety of important genetic applications. The current diploid-based phasing methods are costly and only produce haplotype fragments, whereas the alternatives based on analysis of haploid gametes, which are still in their early development stage, are computationally challenging and error-prone. In this study, we developed an innovative method, named Hapi (pronounced happy), for a fully-automatic inference of chromosomal haplotypes for individual diploid genome using only 3 - 5 gametes, given the heterozygous loci are known for the genome of the individual. Analyses of simulated data and real gamete datasets showed that Hapi outperformed the other two haploid-based methods in terms of accuracy, reliability, and cost efficiency. This highly cost-effective phasing method will increase power of widely employed genome-wide association studies (GWASs) by revealing novel haplotype variants that are entirely undetectable by conventional GWAS, and facilitate animal and plant breeding. Moreover, Hapi can detect meiotic recombination in gametes, which has promise for adoption in the public health sector including the diagnosis of abnormal recombination activity in human reproductive cells, which can aid in reducing infant mortality, birth defects, and miscarriages.

Prof. Zhenyu (Arthur) Jia