Our results suggest that the GABRA2 haplotype block containing rs279858 harbors a functional polymorphism with regulatory effects that influence the expression of all four GABAA-subunit genes on chr4p12 in parallel. These results are consistent with other work suggesting the presence of multi-gene locus control elements within the 4p12 and 5q34 GABAA subunit gene clusters. In two independently derived mouse GABRA6 knockout lines, in which neomycin insertion cassettes were used to target exon 8 of GABRA6, expression of the two adjacent genes, GABRA1 and GABRB2, was reduced in the forebrain, suggesting the presence of a locus control element in the chromosome 5q34 GABAA gene cluster (Uusi-Oukari et al., 2000). In addition, human and primate studies provide evidence of a coordinated developmental switch in the relative expression of GABAA subunits (Fillman et al., 2010, Hashimoto et al., 2009).
