Assignment of the gene GRM1 coding for metabotropic glutamate receptor 1 to human chromosome band 6q24 by in situ hybridization.

Abstract

Metabotropic glutamate receptors (mGluRs) are important modulators of synaptic transmission and have been implicated in epilepsy, neurotoxicity and neurodegenerative disorders (Schoepp and Conn, 1993). Based on amino acid sequence similarity and agonist selectivity, mGluRs are divided into three groups (Pin and Duvoisin, 1995). Subtype mGluR1 classified as group I has been shown to stimulate the phosphoinositide hydrolysis pathway (Schoepp and Conn, 1993). Mice lacking the mGluR1 gene develop ataxic gait and intention tremor (Aiba et al., 1994). Previously, the human gene for mGluR1 (GRM1) was mapped on chromosome 6 by Southern hybridization using human/rodent somatic cell hybrids (Stephan et al., 1996) and radiation hybrid mapping placed this gene between the markers D6S453 and D6S311, about a 4-cM interval on 6q (G3 Map; www.ncbi.nlm.nih.gov/genemap99). Chromosome band 6q24 contains one of the loci for schizoaffective disorder (Kaufmann et al., 1998) and also the locus for Lafora type epilepsy (Sainz et al., 1997). Using a BAC/YAC based physical map constructed for the 6q24 region (Ganesh et al., unpublished) we refined the chromosome position of GRM1. We show that GRM1 is located on chromosome band 6q24, near the genetic marker D6S1480 but distal to EPM2A, a gene recently shown to be involved in Lafora disease (Minassian et al., 1998). Interestingly, GRIK2, the gene for ionotropic glutamate receptor kainate 2, is also located on 6q, at 6q16.3→q21 (Paschen et al., 1994). Materials and methods