GENOMIC CLONING AND LOCALIZATION BY FISH AND LINKAGE ANALYSIS OF THE HUMAN GENE ENCODING THE PRIMARY SUBUNIT NMDAR1 (GRIN1) OF THE NMDA RECEPTOR-CHANNEL

A cDNA clone of the NMDAR1 (isoform E) has been used to screen both la mbda and cosmid genomic libraries. A genomic phage clone was identifie d and sequenced and was found to contain some of the 3' coding regions of the GRIN1 gene. This clone was used to localize the gene using flu orescent in situ hybridization (FISH) to normal chromosomes, and also to a lymphoblastoid cell line containing a translocation involving chr omosomes 9 and 15. FISH localized the gene to chromosome 9q34.3. The c lone was used to screen a panel of genomic DNAs cut with 20 restrictio n enzymes. A VNTR sequence 5' to the gene, which was polymorphic for a number of restriction enzymes, was detected. A PvuII fragment of the genomic clone was found to detect the VNTR on Southern hybridization. The polymorphic VNTR marker was mapped against chromosome 9q34 markers using linkage analysis in the CEPH families. The GRIN1 gene was linke d to D9S7 with a maximum lod score of 20.09 at zero recombination frac tion in males and 0.03% recombination in females.