GENETIC AND PHYSICAL MAPPING OF THE GLUR5 GLUTAMATE-RECEPTOR GENE ON HUMAN-CHROMOSOME-21

Glutamate receptors (GluRs) mediate excitatory neurotransmission and m ay have important roles in central nervous system disorders. To charac terize the human GLUR5 gene, which is located on human chromosome 21q2 2.1, we isolated cDNAs, genomic phage lambda clones, and yeast artific ial chromosomes (YACs) and developed sequence tagged sites (STSs) and simple sequence length polymorphisms (SSLPs) for GLUR5. Genetic mappin g with a tetranucleotide AGAT repeat named GLUR5/AGAT (six alleles obs erved, 70% heterozygosity) placed GLUR5 5 cM telomeric to APP (D21S210 ) and 3cM centromeric to SOD1 (D21S223). The human GLUR5 gene is locat ed near the familial amyotrophic lateral sclerosis (FALS) locus; linka ge analysis of GLUR5 SSLPs in FALS pedigrees yielded negative lod scor es, consistent with the recent association of the FALS locus with the SOD1 gene. Physical mapping of GLUR5 using a YAC contig suggested that the GLUR5 gene spans approximately 400-500kb, and is within 280kb of D21S213. The large size of the GLUR5 gene raises questions regarding i ts functional significance. Our GLUR5 YAC contig includes clones found in the Genethon chromosome 21 YAC contig, and reference to the larger contig indicates the orientation centromere - D21S213 - GLUR5 5' end- GLUR5/AGAT - GLUR5 3'- end - SOD1. The development of GLUR5/AGAT shoul d permit rapid determination of the status of the GLUR5 gene in indivi duals with partial trisomy or monosomy of chromosome 21. Such studies may provide insights concerning the possible role of GLUR5 in Down syn drome.