Mapping of the α 4 subunit gene (GABRA4) to human chromosome 4 defines an α 2—α 4—β 1—γ 1 gene cluster: further evidence that modern GABA A receptor gene clusters are derived from an ancestral cluster

Abstract

We demonstrated previously that an α 1—β 2—γ 2 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 α 4 gene (GABRA4) maps to human chromosome 4p14–q12, defining a cluster comprising the α 2, α 4, β 1, and γ 1 genes. The existence of an α 2—α 4—β 1—γ 1 cluster on chromosome 4 and an α 1—α 6—β 2—γ 2 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 α 5—α x —β 3—γ 3 gene cluster at the locus for Angelman and Prader—Willi syndromes.