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Originally published as Genetics Published Articles Ahead of Print on January 16, 2005.
Genetics, Vol. 169, 1763-1777, March 2005, Copyright © 2005
doi:10.1534/genetics.104.032219
Statistical Tests of the Coalescent Model Based on the Haplotype Frequency Distribution and the Number of Segregating Sites
Hideki Innan*,
Kangyu Zhang
,
Paul Marjoram
,
Simon Tavaré,
and
Noah A. Rosenberg,1
* Human Genetics Center, School of Public Health, University of Texas Health Science Center, Houston, Texas 77030
Program in Molecular and Computational Biology, University of Southern California, Los Angeles, California 90089-1113
Department of Preventive Medicine, University of Southern California, Los Angeles, California 90089-9011
Department of Oncology, University of Cambridge, Hutchison/MRC Research Centre, Cambridge CB2 2XZ, United Kingdom
1 Corresponding author: Program in Molecular and Computational Biology, University of Southern California, Los Angeles, CA 90089-1113.
E-mail: noahr{at}usc.edu
Several tests of neutral evolution employ the observed number of segregating sites and properties of the haplotype frequency distribution as summary statistics and use simulations to obtain rejection probabilities. Here we develop a "haplotype configuration test" of neutrality (HCT) based on the full haplotype frequency distribution. To enable exact computation of rejection probabilities for small samples, we derive a recursion under the standard coalescent model for the joint distribution of the haplotype frequencies and the number of segregating sites. For larger samples, we consider simulation-based approaches. The utility of the HCT is demonstrated in simulations of alternative models and in application to data from Drosophila melanogaster.
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