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.