RT Journal Article
SR Electronic
T1 Conditional Probability Methods for Haplotyping in Pedigrees
JF Genetics
JO Genetics
FD Genetics Society of America
SP 2055
OP 2065
DO 10.1534/genetics.103.021055
VO 167
IS 4
A1 Gao, Guimin
A1 Hoeschele, Ina
A1 Sorensen, Peter
A1 Du, Fengxing
YR 2004
UL http://www.genetics.org/content/167/4/2055.abstract
AB 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.