MODELS FOR HAPLOTYPE EVOLUTION IN A NONSTATIONARY POPULATION

Haplotype mapping has emerged in the past few years as a powerful tool for the fine mapping of disease genes, it is typically carried out on a sample of affected individuals from a population isolate. If the ch romosome neighborhood of a disease gene is saturated with markers, the n each new mutation in the population or existing mutation introduced by a population founder exhibits a unique haplotype signature at the t ime of its introduction. Partial disruptions of these signatures by re combination can be visualized in affecteds and provide important clues to the location of the disease gene, The current paper models haploty pe evolution with the intention of clarifying the most favorable circu mstances for haplotype mapping. Comparisons with linkage mapping are s tressed. For dominant diseases, both deterministic and stochastic mode ls are suggested. Numerical examples based on Finnish population param eters illustrate the general theory in the presence of the complicatio ns of selection, mutation, and slow, exponential growth of the isolate , (C) 1998 Academic Press.