This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taylor, J. A. Articles by Morris, R. W. Search for Related Content PubMed PubMed Citation Articles by Taylor, J. A. Articles by Morris, R. W.

How Well Do HapMap Haplotypes Identify Common Haplotypes of Genes? A Comparison with Haplotypes of 334 Genes Resequenced in the Environmental Genome Project

¹ Laboratory of Molecular Carcinogenesis, ² Epidemiology Branch, and ³ Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park; and ⁴ Department of Anesthesiology, Duke University Medical Center, Durham, North Carolina

Requests for reprints: Jack A. Taylor, National Institute of Environmental Health Science, MD A3-05, 111 Alexander Drive, P.O. Box 12233, Research Triangle Park, NC 27709. Phone: 919-541-4631; Fax: 919-541-2511. E-mail: taylor{at}niehs.nih.gov

One of the goals of the International HapMap Project is the identification of common haplotypes in genes. However, HapMap uses an incomplete catalogue of single nucleotide polymorphisms (SNPs) and might miss some common haplotypes. We examined this issue using data from the Environmental Genome Project (EGP) which resequenced 335 genes in 90 people, and thus, has a nearly complete catalogue of gene SNPs. The EGP identified a total of 45,243 SNPs, of which 10,780 were common SNPs (minor allele frequency 0.1). Using EGP common SNP genotype data, we identified 1,459 haplotypes with frequency 0.05 and we use these as "benchmark" haplotypes. HapMap release 16 had genotype information for 1,573 of 10,780 (15%) EGP common SNPs. Using these SNPs, we identified common HapMap haplotypes (frequency 0.05) in each of the four HapMap ethnic groups. To compare common HapMap haplotypes to EGP benchmark haplotypes, we collapsed benchmark haplotypes to the set of 1,573 SNPs. Ninety-eight percent of the collapsed benchmark haplotypes could be found as common HapMap haplotypes in one or more of the four HapMap ethnic groups. However, collapsing benchmark haplotypes to the set of SNPs available in HapMap resulted in a loss of haplotype information: 545 of 1,459 (37%) benchmark haplotypes were uniquely identified, and only 25% of genes had all their benchmark haplotypes uniquely identified. We resampled the EGP data to examine the effect of increasing the number of HapMap SNPs to 5 million, and estimate that 40% of common SNPs in genes will be sampled and that half of the genes will have sufficient SNPs to identify all common haplotypes. This inability to distinguish common haplotypes of genes may result in loss of power when examining haplotype-disease association. (Cancer Epidemiol Biomarkers Prev 2006;15(1):133–7)

This article has been cited by other articles:

				C. I. Amos Successful design and conduct of genome-wide association studies Hum. Mol. Genet., October 15, 2007; 16(R2): R220 - R225. [Abstract] [Full Text] [PDF]

				J. Lu, Q. Wei, M. L. Bondy, D. Li, A. Brewster, S. Shete, T.-K. Yu, A. Sahin, F. Meric-Bernstam, K. K. Hunt, et al. Polymorphisms and haplotypes of the NBS1 gene are associated with risk of sporadic breast cancer in non-Hispanic white women <=55 years Carcinogenesis, November 1, 2006; 27(11): 2209 - 2216. [Abstract] [Full Text] [PDF]