Conditional probability methods for haplotyping in pedigrees.

Abstract:

:Efficient haplotyping in pedigrees is important for the fine mapping of quantitative trait locus (QTL) or complex disease genes. To reconstruct haplotypes efficiently for a large pedigree with a large number of linked loci, two algorithms based on conditional probabilities and likelihood computations are presented. The first algorithm (the conditional probability method) produces a single, approximately optimal haplotype configuration, with computing time increasing linearly in the number of linked loci and the pedigree size. The other algorithm (the conditional enumeration method) identifies a set of haplotype configurations with high probabilities conditional on the observed genotype data for a pedigree. Its computing time increases less than exponentially with the size of a subset of the set of person-loci with unordered genotypes and linearly with its complement. The size of the subset is controlled by a threshold parameter. The set of identified haplotype configurations can be used to estimate the identity-by-descent (IBD) matrix at a map position for a pedigree. The algorithms have been tested on published and simulated data sets. The new haplotyping methods are much faster and provide more information than several existing stochastic and rule-based methods. The accuracies of the new methods are equivalent to or better than those of these existing methods.

journal_name

Genetics

journal_title

Genetics

authors

Gao G,Hoeschele I,Sorensen P,Du F

doi

10.1534/genetics.103.021055

keywords:

subject

Has Abstract

pub_date

2004-08-01 00:00:00

pages

2055-65

issue

4

eissn

0016-6731

issn

1943-2631

pii

167/4/2055

journal_volume

167

pub_type

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