HAPLOTYPE INFERENCE USING PEDIGREE DATA

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. We study the haplotype inference problem from pedigree data under the zero recombination assumption, which is well supported by real data for tightly linked markers (i.e. single nucleotide polymorphisms (SNPs)) over a relatively large chromosome segment. We solve the problem in a rigorous mathematical manner by formulating genotype constraints as a linear system of inheritance variables. We then utilize disjoint-set structures to encode connectivity information among individuals, to detect constraints from genotypes, and to check consistency of constraints. On a tree pedigree without missing data, our algorithm can output a general solution as well as the number of total specific solutions in a nearly linear time O(mn . alpha(n)), where m is the number of loci, n is the number of individuals and alpha is the inverse Ackermann function, which is a further improvement over existing ones. We also extend the idea to looped pedigrees and pedigrees with missing data by considering existing (partial) constraints on inheritance variables.