Mapping of the α₄ subunit gene (GABRA4) to human chromosome 4 defines an α₂-α₄-β₁-γ₁ gene cluster: further evidence that modern GABA_A receptor gene clusters are derived from an ancestral cluster

We demonstrated previously that an α₁-β₂-γ₂ gene cluster of the γ-aminobutyric acid (GABA_A) receptor is located on human chromosome 5q34-q35 and that an ancestral α-β-γ gene cluster probably spawned clusters on chromosomes 4, 5, and 15. Here, we report that the α₄ gene (GABRA4) maps to human chromosome 4p14-q12, defining a cluster comprising the α₂, α₄, β₁, and γ₁ genes. The existence of an α₂-α₄-β₁-γ₁ cluster on chromosome 4 and an α₁-α₆-β₂-γ₂ cluster on chromosome 5 provides further evidence that the number of ancestral GABA_A receptor subunit genes has been expanded by duplication within an ancestral gene cluster. Moreover, if duplication of the α gene occurred before duplication of the ancestral gene cluster, then a heretofore undiscovered subtype of α subunit should be located on human chromosome 15q11-q13 within an α₅-α_x-β₃-γ₃ gene cluster at the locus for Angelman and Prader-Willi syndromes.