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Bayesian Analysis of Haplotypes for Linkage Disqeuilibrium Mapping



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Methods Bayesian Analysis of Haplotypes for Linkage Disequilibrium Mapping Jun S Liu 1 6 Chiara Sabatti 2 Jun Teng 3 Bronya J B Keats 4 and Neil Risch5 1 Department of Statistics Harvard University Cambridge Massachusetts 02138 USA 2Department of Statistics University of California Los Angeles California 90095 USA 3JP Morgan New York New York 10036 USA 4Louisiana State University Department of Genetics Health Science Center New Orleans Louisiana 70112 USA 5Department of Genetics Stanford University Stanford California 94305 USA Haplotype analysis of disease chromosomes can help identify probable historical recombination events and localize disease mutations Most available analyses use only marginal and pairwise allele frequency information We have developed a Bayesian framework that utilizes full haplotype information to overcome various complications such as multiple founders unphased chromosomes data contamination and incomplete marker data A stochastic model is used to describe the dependence structure among several variables characterizing the observed haplotypes for example the ancestral haplotypes and their ages mutation rate recombination events and the location of the disease mutation An efficient Markov chain Monte Carlo algorithm was developed for computing the estimates of the quantities of interest The method is shown to perform well in both real data sets cystic fibrosis data and Friedreich ataxia data and simulated data sets The program that implements the proposed method BLADE as well as the two real datasets can be obtained from http www fas harvard edu junliu TechRept 01folder diseq prog tar gz In the quest to identify genes responsible for specific illnesses it has been observed in many cases that a large portion of the carriers of the disease gene in the current population are descendant from a small number of founders in whose genomes the deleterious mutation appeared some generations ago This translates into inhomogeneity between the allele



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