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Polymorphism analysis of six selenoprotein genes: support for a selective sweep at the glutathione peroxidase 1 locus (3p21) in Asian populations

Charles B Foster12*, Kshama Aswath2, Stephen J Chanock34, Heather F McKay2 and Ulrike Peters56

Author Affiliations

1 Section of Pediatric Infectious Diseases, Division of Pediatrics, Desk A120, The Children's Hospital, The Cleveland Clinic, 9500 Euclid Avenue, Cleveland, OH 44195, USA

2 Division of Pediatric Infectious Diseases, Department of Pediatrics, Johns Hopkins University, 600 North Wolfe Street, Park 256, Baltimore, MD, 21287, USA

3 Section of Genomic Variation, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD, 20892, USA

4 Core Genotyping Facility, Advanced Technology Center, National Cancer Institute, Bethesda, MD, 20892, USA

5 Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Department of Health and Human Services, Rockville, Maryland, USA

6 Cancer Prevention Program, Fred Hutchinson Cancer Research Center, Seattle, WA, 98109, USA

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BMC Genetics 2006, 7:56  doi:10.1186/1471-2156-7-56

Published: 11 December 2006



There are at least 25 human selenoproteins, each characterized by the incorporation of selenium into the primary sequence as the amino acid selenocysteine. Since many selenoproteins have antioxidant properties, it is plausible that inter-individual differences in selenoprotein expression or activity could influence risk for a range of complex diseases, such as cancer, infectious diseases as well as deleterious responses to oxidative stressors like cigarette smoke. To capture the common genetic variants for 6 important selenoprotein genes (GPX1, GPX2, GPX3, GPX4, TXNRD1, and SEPP1) known to contribute to antioxidant host defenses, a re-sequence analysis was conducted across these genes with particular interest directed at the coding regions, intron-exon borders and flanking untranslated regions (UTR) for each gene in an 102 individual population representative of 4 major ethnic groups found within the United States.


For 5 of the genes there was no strong evidence for selection according to the expectations of the neutral equilibrium model of evolution; however, at the GPX1 locus (3p21) there was evidence for positive selection. Strong confirmatory evidence for recent positive selection at the genomic region 3p21 in Asian populations is provided by data from the International HapMap project.


The SNPs and fine haplotype maps described in this report will be valuable resources for future functional studies, for population specific genetic studies designed to comprehensively explore the role of selenoprotein genetic variants in the etiology of various human diseases, and to define the forces responsible for a recent selective sweep in the vicinity of the GPX1 locus.