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Hidden Markov Dirichlet Process: Modeling Genetic Recombination in Open Ancestral Space

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3 Author(s)

We present a new statistical framework called hidden Markov Dirichlet process (HMDP) to jointly model the genetic recombinations among possibly infinite number of founders and the coalescence-with-mutation events in the resulting genealogies. The HMDP posits that a haplotype of genetic markers is generated by a sequence of recombination events that select an ancestor for each locus from an unbounded set of founders according to a 1st-order Markov transition process. Conjoining this process with a mutation model, our method accommodates both between-lineage recombination and within-lineage sequence variations, and leads to a compact and natural interpretation of the population structure and inheritance process underlying haplotype data. We have developed an efficient sampling algorithm for HMDP based on a two-level nested Pólya urn scheme. On both simulated and real SNP haplotype data, our method performs competitively or significantly better than extant methods in uncovering the recombination hotspots along chromosomal loci; and in addition it also infers the ancestral genetic patterns and offers a highly accurate map of ancestral compositions of modern populations.