Genetics. Published Articles Ahead of Print: December 15, 2005, Copyright © 2005
doi:10.1534/genetics.105.042978


A more recent version of this article appeared on April 1, 2006.


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Modeling Haplotype Block Variation using Markov Chains

1 Technion--Israel Institute of Technology

* To whom correspondence should be addressed. E-mail: gdg{at}cs.technion.ac.il.

Submitted on March 7, 2005
Revised on April 12, 2005
Accepted on 23 November 2005


Abstract

Models of background variation in genomic regions form the basis of linkage disequilibrium mapping methods. In this work we analyze a background model which groups SNPs into haplotype blocks and represents the dependencies between blocks by a Markov chain. We develop an error measure to compare the performance of this model against the common model which assumes blocks are independent. By examining data from the International Haplotype Mapping project, we show how the Markov model over haplotype blocks is most accurate when representing blocks in strong linkage disequilibrium. This contrasts with the independent model which is rendered less accurate by linkage disequilibrium. We provide a theoretical explanation for this surprising property of the Markov model and relate its behavior to allele diversity.

Key Words: LD mapping, Markov models, haplotype blocks, linkage disequilibrium, recombination hotspots