Mapping of the beta 2 subunit gene (GABRB2) to microdissected human chromosome 5q34-q35 defines a gene cluster for the most abundant GABAA receptor isoform.
The gamma-aminobutyric acid receptor (GABAAR) is a multisubunit Cl- channel that mediates most fast inhibitory synaptic transmission in the central nervous system. Molecular evolution has given rise to many genetic variants of GABAAR subunits, including alpha 1-6, beta 1-4, gamma 1-4, delta, and rho 1-2, suggesting that an enormous number of combinations of subunits are possible. Here we report that the beta 2 gene is located on chromosome 5q34-q35, defining a cluster comprising alpha 1, beta 2, and gamma 2 genes that together code for the most abundant GABAAR isoform. The fact that intron position is conserved in the beta 1-3 genes, taken together with the observation that chromosomes 4 and 15 also contain distinct alpha-beta-gamma gene clusters, strongly suggests that an ancestral alpha-beta-gamma cluster was duplicated and translocated to at least two different chromosomes. This organization of GABAAR gene clusters may have been preserved as linkage provides a mechanism for facilitating coordinate gene expression.
Russek
S J
SJ
Department of Pharmacology, Boston University School of Medicine, Massachusetts 02118.
Farb
D H
DH
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D002645:Chickens; D002874:Chromosome Mapping; D002895:Chromosomes, Human, Pair 5; D017124:Conserved Sequence; D017931:DNA Primers; D005091:Exons; D015186:Hominidae / Q000235:genetics*; D006801:Humans; D006822:Hybrid Cells; D007438:Introns; D046911:Macromolecular Substances; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D016133:Polymerase Chain Reaction; D051381:Rats; D011963:Receptors, GABA-A / Q000096:biosynthesis / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D046911:Macromolecular Substances; D011963:Receptors, GABA-A