Bayesian Analysis of Haplotypes for Linkage Disequilibrium Mapping
- 1Department 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
Abstract
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 fromhttp://www.fas.harvard.edu/∼junliu/TechRept/01folder/diseq_prog.tar.gz.
Footnotes
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↵6 Corresponding author.
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E-MAIL jliu{at}stat.harvard.edu; FAX (617) 496-8057.
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Article and publication are at http://www.genome.org/cgi/doi/10.1101/gr.194801.
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- Received May 2, 2001.
- Accepted July 30, 2001.
- Cold Spring Harbor Laboratory Press
