SCIENCE@home

Sequence variation and linkage disequilibrium in the GABA transporter-1 gene (SLC6A1) in five populations: implications for pharmacogenetic research

Rungnapa Hirunsatit,Risto Ilomäki,R. Malison,P. Räsänen,Essi Ilomäki,H. Kranzler,T. Kosten,A. Sughondhabirom,N. Thavichachart,S. Tangwongchai,J. Listman,A. Mutirangura,J. Gelernter,J. Lappalainen

Published 2007 in BMC Genetics

ABSTRACT

BackgroundGABA transporter-1 (GAT-1; genetic locus SLC6A1) is emerging as a novel target for treatment of neuropsychiatric disorders. To understand how population differences might influence strategies for pharmacogenetic studies, we identified patterns of genetic variation and linkage disequilibrium (LD) in SLC6A1 in five populations representing three continental groups.ResultsWe resequenced 12.4 kb of SLC6A1, including the promoters, exons and flanking intronic regions in African-American, Thai, Hmong, Finnish, and European-American subjects (total n = 40). LD in SLC6A1 was examined by genotyping 16 SNPs in larger samples. Sixty-three variants were identified through resequencing. Common population-specific variants were found in African-Americans, including a novel 21-bp promoter region variable number tandem repeat (VNTR), but no such variants were found in any of the other populations studied. Low levels of LD and the absence of major LD blocks were characteristic of all five populations. African-Americans had the highest genetic diversity. European-Americans and Finns did not differ in genetic diversity or LD patterns. Although the Hmong had the highest level of LD, our results suggest that a strategy based on the use of tag SNPs would not translate to a major improvement in genotyping efficiency.ConclusionOwing to the low level of LD and presence of recombination hotspots, SLC6A1 may be an example of a problematic gene for association and haplotype tagging-based genetic studies. The 21-bp promoter region VNTR polymorphism is a putatively functional candidate allele for studies focusing on variation in GAT-1 function in the African-American population.

PUBLICATION RECORD

CITATION MAP

EXTRACTION MAP

CLAIMS

  • No claims are published for this paper.

CONCEPTS

  • No concepts are published for this paper.

REFERENCES

Showing 1-37 of 37 references · Page 1 of 1

CITED BY

Showing 1-7 of 7 citing papers · Page 1 of 1