Interpopulation linkage disequilibrium patterns of GABRA2 and GABRG1 genes at the GABA cluster locus on human chromosome 4

GABRA2 and GABRG1, which encode the α-2 and γ-1 subunits, respectively, of the GABA A receptor, are located in a cluster on chromosome 4p. The GABRA2 locus has been found to be associated with alcohol dependence in several studies, but no functional variant that can account for this association has...

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Published in:Genomics (San Diego, Calif.) Calif.), 2008, Vol.91 (1), p.61-69
Main Authors: Ittiwut, Chupong, Listman, Jennifer, Mutirangura, Apiwat, Malison, Robert, Covault, Jonathan, Kranzler, Henry R., Sughondhabirom, Atapol, Thavichachart, Nuntika, Gelernter, Joel
Format: Article
Language:English
Subjects:
Adolescent
Adult
Alcohol dependence
Alcohol-Related Disorders - genetics
Alcoholism and acute alcohol poisoning
Biological and medical sciences
Chromosomes, Human, Pair 4 - genetics
DNA, Intergenic - genetics
Female
Fundamental and applied biological sciences. Psychology
GABRA2
GABRG1
Genes. Genome
Genetic Markers
Genetic Predisposition to Disease
Genetics of eukaryotes. Biological and molecular evolution
Haplotype
Haplotypes
Humans
Linkage disequilibrium
Linkage Disequilibrium - genetics
Male
Medical sciences
Molecular and cellular biology
Molecular genetics
Multigene Family - genetics
Polymorphism, Single Nucleotide
Quantitative Trait Loci - genetics
Receptors, GABA-A - genetics
Thailand
Toxicology
United States
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Summary:GABRA2 and GABRG1, which encode the α-2 and γ-1 subunits, respectively, of the GABA A receptor, are located in a cluster on chromosome 4p. The GABRA2 locus has been found to be associated with alcohol dependence in several studies, but no functional variant that can account for this association has been identified. To understand the reported associations, we sought to understand the linkage disequilibrium (LD) patterns and haplotype structures of these genes. With close intergenic distance, ∼ 90 kb, it was anticipated that some markers might show intergenic LD. Variation in 13-SNP haplotype block structure was observed in five different populations: European American, African American, Chinese (Han and Thai), Thai, and Hmong. In the Hmong, a 280-kb region of considerably higher LD spans the intergenic region, whereas in other populations, there were two or more LD blocks that cross this region. These findings may aid in understanding the genetic association of this locus with alcohol dependence in several populations.
ISSN:0888-7543
1089-8646
DOI:10.1016/j.ygeno.2007.08.007