Linkage disequilibrium is a continuously changing aspect of each population and micro-locale along the genome that reflects the accumulated influences from many sources such as recombination, population, history, selection, genetic drift, mutation, chromosomal region (telomeric to centromeric) effects, etc. The static observation of linkage disequilibrium at one locus in one population cannot adequately represent this dynamic aspect of the organization of variation in the human genome. This Program Project proposes to carry out a systematic evaluation of linkage disequilibrium in a variety of human populations representing the diversity of the species for loci representing diverse chromosomal regions of the genome. The research will involve data collections for different types of markers at twenty autosomal loci in each of twenty populations, and one very long region (one megabase) in three quite diverse populations, theoretical and statistical studies to develop improved analytic approaches, computer simulations as an aid to evaluation of various methodologies and analyses of the data. The unique dataset that will result and the improved analytic methods will allow characterization of systematic features of linkage disequilibrium attributable to effects of population and chromosomal region as well as idiosyncratic features. The resulting overview of the nature and extent of linkage disequilibrium should provide greatly improved guidelines for the wide range of practical applications of linkage disequilibrium that clinical and basic researchers pursue, especially the refining of map locations of disease related genes.
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