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Originally published as Genetics Published Articles Ahead of Print on June 18, 2005.
Genetics, Vol. 171, 259-267, September 2005, Copyright © 2005
doi:10.1534/genetics.105.043075
Haplotype Diversity in 11 Candidate Genes Across Four Populations
T. H. Beaty*,1,
M. D. Fallin*,
J. B. Hetmanski*,
I. McIntosh
,
S. S. Chong
,
R. Ingersoll,
X. Sheng
,
R. Chakraborty and
A. F. Scott
* Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland 21205, Institute of Genetic Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland 21205, Department of Pediatrics, National University of Singapore, Singapore 119260 and Center for Genome Information, University of Cincinnati, Cincinnati, Ohio 45267
1 Corresponding author: Johns Hopkins University, Bloomberg School of Public Health, Department of Epidemiology, 615 N. Wolfe St., Baltimore, MD 21205.
Analysis of haplotypes based on multiple single-nucleotide polymorphisms (SNP) is becoming common for both candidate gene and fine-mapping studies. Before embarking on studies of haplotypes from genetically distinct populations, however, it is important to consider variation both in linkage disequilibrium (LD) and in haplotype frequencies within and across populations, as both vary. Such diversity will influence the choice of "tagging" SNPs for candidate gene or whole-genome association studies because some markers will not be polymorphic in all samples and some haplotypes will be poorly represented or completely absent. Here we analyze 11 genes, originally chosen as candidate genes for oral clefts, where multiple markers were genotyped on individuals from four populations. Estimated haplotype frequencies, measures of pairwise LD, and genetic diversity were computed for 135 European-Americans, 57 Chinese-Singaporeans, 45 Malay-Singaporeans, and 46 Indian-Singaporeans. Patterns of pairwise LD were compared across these four populations and haplotype frequencies were used to assess genetic variation. Although these populations are fairly similar in allele frequencies and overall patterns of LD, both haplotype frequencies and genetic diversity varied significantly across populations. Such haplotype diversity has implications for designing studies of association involving samples from genetically distinct populations.
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