Screening of a genomic DNA library with a portion of the cDNA encoding the γ-aminobutyric acid (GABA) receptor subunit rho1 identified two distinct clones. DNA sequencing revealed that one clone contained a single exon from the rho1 gene (GABBR1) while the second clone encompassed an exon with 96% identity to the rho1 gene. Screening of a human retina cDNA library with oligonucleotides specific for the exon in the second clone identified a 3-kb cDNA with an open reading frame of 1395 bp. The predicted amino acid sequence of this cDNA demonstrates 30 to 38% similarity to α, β, γ, and δ GABA receptor subunits and 74% similarity to the GABA rho1 subunit suggesting that the newly isolated cDNA encodes a new member of the rho subunit family, tentatively named GABA rho2. Polymerase chain reaction (PCR) amplification of rho1 and rho2 gene sequences from DNA of three somatic cell hybrid panels maps both genes to human chromosome 6, bands q14 to q21. Tight linkage was also demonstrated between restriction fragment length variants (RFLVs) from each rho gene and the Tsha locus on mouse chromosome 4, which is homologous to the CGA locus on human chromosome 6q12-q21. These two lines of evidence confirm that GABRR1 and newly identified GABRR2 map to the same region on human chromosome 6. This close physical association and high degree of sequence similarity raises the possibility that one rho gene arose from the other by duplication.
|Number of pages||6|
|State||Published - Apr 1992|
Bibliographical noteFunding Information:
We thank the following individuals who kindly provided clones: Dr. D. Nathans (deposited with American Tissue Type Culture Collection) (JAC.l), Dr. D. Givol (pMS-l), and Dr. P. Guyton and I. A. Kourides (cDNA clone for T&a). We are grateful to Dr. T. Mohandas, Dr. C.-H. Grezchik and Dr. J. J. Wasmuth for providing valuable cell lines, Dr. E. Jabs for DNA from hybrid cell lines (NIH HG00373), Dr. J. Nathans for the retina cDNA library, Dr. Caroline Hayward for HLA-DR@l oligonucleotide primers, Thad Howard for skilled technical assistance, and Barbara Shaffer for secretarial assistance. This work is supported by grants from the NIH (G.R.C., H.Y.Z. [NS27699] and M.F.S. [HGOOlDl]) and CF Foundation (G.R.C.). G.R.C. is a Merck Clinician Scientist.
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