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Originally published as Genetics Published Articles Ahead of Print on July 29, 2007.

Genetics, Vol. 177, 1101-1116, October 2007, Copyright © 2007
doi:10.1534/genetics.107.074047

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Haplotype Inference in General Pedigrees Using the Cluster Variation Method

Cornelis A. Albers*,1, Tom Heskes{dagger} and Hilbert J. Kappen*

* Department of Cognitive Neuroscience/Biophysics, Institute for Computing and Information Sciences, Radboud University, 6525 EZ Nijmegen, The Netherlands and {dagger} Department of Information and Knowledge Systems, Institute for Computing and Information Sciences, Radboud University, 6525 ED Nijmegen, The Netherlands

1 Corresponding author: Department of Cognitive Neuroscience/Biophysics/126, Institute for Computing and Information Sciences, Radboud University, Geert Grooteplein 21, 6525 EZ Nijmegen, The Netherlands.
E-mail: k.albers{at}science.ru.nl

We present CVMHAPLO, a probabilistic method for haplotyping in general pedigrees with many markers. CVMHAPLO reconstructs the haplotypes by assigning in every iteration a fixed number of the ordered genotypes with the highest marginal probability, conditioned on the marker data and ordered genotypes assigned in previous iterations. CVMHAPLO makes use of the cluster variation method (CVM) to efficiently estimate the marginal probabilities. We focused on single-nucleotide polymorphism (SNP) markers in the evaluation of our approach. In simulated data sets where exact computation was feasible, we found that the accuracy of CVMHAPLO was high and similar to that of maximum-likelihood methods. In simulated data sets where exact computation of the maximum-likelihood haplotype configuration was not feasible, the accuracy of CVMHAPLO was similar to that of state of the art Markov chain Monte Carlo (MCMC) maximum-likelihood approximations when all ordered genotypes were assigned and higher when only a subset of the ordered genotypes was assigned. CVMHAPLO was faster than the MCMC approach and provided more detailed information about the uncertainty in the inferred haplotypes. We conclude that CVMHAPLO is a practical tool for the inference of haplotypes in large complex pedigrees.




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M. Abney
Identity-by-Descent Estimation and Mapping of Qualitative Traits in Large, Complex Pedigrees
Genetics, July 1, 2008; 179(3): 1577 - 1590.
[Abstract] [Full Text] [PDF]


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