A block-free hidden Markov model for genotypes and its application to disease association

We present a new stochastic model for genotype generation. The model offers a compromise between rigid block structure and no structure altogether: It reflects a general blocky structure of haplotypes, but also allows for "exchange" of haplotypes at nonboundary SNP sites; it also accommodates rare haplotypes and mutations. We use a hidden Markov model and infer its parameters by an expectation-maximization algorithm. The algorithm was implemented in a software package called HINT (haplotype inference tool) and tested on 58 datasets of genotypes. To evaluate the utility of the model in association studies, we used biological human data to create a simple disease association search scenario. When comparing HINT to three other models, HINT predicted association most accurately.