Determining linkage phase from population samples with statistical methods is accurate only within regions of high linkage disequilibrium (LD). Yet, affected individuals in a genetic mapping study, including those involving cases and controls, may share sequences identical-by-descent stretching on the order of 10s to 100s of kilobases, quite possibly over regions of low LD in the population. At the same time, inferring phase from nuclear families may be hampered by missing family members, missing genotypes, and the noninformativity of certain genotype patterns. In this study, we reformulate our previous haplotype reconstruction algorithm, and its associated computer program, to phase parents with information derived from population samples as well as from their offspring. In applications of our algorithm to 100-kb stretches, simulated in accordance to a Wright-Fisher model with typical levels of LD in humans, we find that phase reconstruction for 160 trios with 10% missing data is highly accurate (>90%) over the entire length. Furthermore, our algorithm can estimate allelic status for missing data at high accuracy (>95%). Finally, the input capacity of the program is vast, easily handling thousands of segregating sites in ≥1000 chromosomes.
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