Polymorphisms and intron sequences flanking the alternatively spliced 8-amino-acid exon of γ2 subunit gene for GABAA receptors

Gamma-amminobutyric acid (GABA) is a major inhibitory neurotransmitter. Two alternatively spliced forms of the γ2 subunit of GABAA receptor (γ2L and γ2S), which differ by an exon of eight amino acids, show different sensitivities to modulatory effects of ethanol on receptor activities. A 2.7 kb DNA fragment and an 1.7 kb DNA fragment covering respectively the introns upstream and downstream from the 8-amino-acid exon were obtained through PCR amplification of human genomic DNA using primers derived from cDNA sequences. Total sequencing of these fragments showed a composite 4.2 kb segment containing the 8-amino-acid exon and consensus sequences for RNA splice junctions. Restriction fragment length polymorphisms (RFLP) based on NciI restriction digestion were found among Chinese in Taiwan. This RFLP provides a useful DNA marker for allelic association or linkage analyses of the role of GABAA receptors in predisposition to alcoholism or other neuropsychiatric disorders.