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Title: Localization of a gene for a glutamate binding subunit of a NMDA receptor (GRINA) to 8q24

Abstract

This article reports on the localization of a gene for a glutamate binding subunit of an N-methyl-D-aspartate (NMDA) receptor, called GRINA, to human chromosome 8q24 using fluorescence in situ hybridization and radiation hybridization mapping. This gene mapped outside the critical region for benign familial neonatal convulsions (BFNC), a rare form of epilepsy; however, GRINA could be the causative genetic factor inducing idiopathic generalized epilepsy. Further studies need to be conducted. 15 refs., 2 figs.

Authors:
; ;  [1]
  1. Univ. of Texas Health Science Center, San Antonio, TX (United States) [and others
Publication Date:
OSTI Identifier:
466407
Resource Type:
Journal Article
Resource Relation:
Journal Name: Genomics; Journal Volume: 32; Journal Issue: 1; Other Information: PBD: 15 Feb 1996
Country of Publication:
United States
Language:
English
Subject:
55 BIOLOGY AND MEDICINE, BASIC STUDIES; GENES; DNA-CLONING; GENETIC MAPPING; DNA SEQUENCING; MUTATION FREQUENCY; GENE MUTATIONS; R CODES; RESOLUTION; HUMAN CHROMOSOME 8; EPILEPSY; PATHOGENESIS; NEONATES; HEREDITARY DISEASES; FLUORESCENCE; DNA HYBRIDIZATION; NUCLEOTIDES; RADIATION INDUCED MUTANTS; TELOMERES; BIOLOGICAL MARKERS; DOMINANT MUTATIONS; PROBES; POLYMERASE CHAIN REACTION

Citation Formats

Lewis, T.B., DuPont, B.R., and Leach, R.. Localization of a gene for a glutamate binding subunit of a NMDA receptor (GRINA) to 8q24. United States: N. p., 1996. Web. doi:10.1006/geno.1996.0088.
Lewis, T.B., DuPont, B.R., & Leach, R.. Localization of a gene for a glutamate binding subunit of a NMDA receptor (GRINA) to 8q24. United States. doi:10.1006/geno.1996.0088.
Lewis, T.B., DuPont, B.R., and Leach, R.. 1996. "Localization of a gene for a glutamate binding subunit of a NMDA receptor (GRINA) to 8q24". United States. doi:10.1006/geno.1996.0088.
@article{osti_466407,
title = {Localization of a gene for a glutamate binding subunit of a NMDA receptor (GRINA) to 8q24},
author = {Lewis, T.B. and DuPont, B.R. and Leach, R.},
abstractNote = {This article reports on the localization of a gene for a glutamate binding subunit of an N-methyl-D-aspartate (NMDA) receptor, called GRINA, to human chromosome 8q24 using fluorescence in situ hybridization and radiation hybridization mapping. This gene mapped outside the critical region for benign familial neonatal convulsions (BFNC), a rare form of epilepsy; however, GRINA could be the causative genetic factor inducing idiopathic generalized epilepsy. Further studies need to be conducted. 15 refs., 2 figs.},
doi = {10.1006/geno.1996.0088},
journal = {Genomics},
number = 1,
volume = 32,
place = {United States},
year = 1996,
month = 2
}
  • A role for the N-methyl-D-aspartate (NMDA) receptor in the molecular pathology underlying Huntington disease (HD) has been proposed on the basis of neurochemical studies in HD and the ability of the NMDA receptor to mediate neuronal cell death. The molecular cloning of the human NMDA receptor subunit (NMDAR1) and a proposed glutamate-binding subunit of the NMDA receptor (NMDARA1) have provided an opportunity to test the hypothesis that either of these genes might be directly involved in the causation of HD. The authors have mapped NMDAR1 to 9q34.3 using in situ hybridization studies and NMDARA1 to human chromosome 8 using amore » somatic cell hybrid panel. Because the gene causing HD has been localized to chromosome 4p16.3, the chromosome assignments reported here are inconsistent with either of these genes playing a causative role in the molecular pathology of HD. However, it is noteworthy that the gene for torsion dystonia has also been localized by genetic studies to 9q34.3, the same regional map location as NMDAR1. 12 refs., 1 tab.« less
  • The authors isolated a human glutamate receptor subunit 7 (GluR-7) cosmid after high stringency screening of a human genomic placental library using a rat GluR-7 cDNA as a probe. A 614-bp fragment of the GluR-7 cosmid was sequenced, and an exon that encodes 53 amino acids was found between two introns. The exon exhibited 89% and 96% identity at the nucleotide and amino acid levels, respectively, with the corresponding region of rat GluR-7. The human GluR-7 was classified as a kainate subtype glutamate receptor based on its homology to rat GluR07. Using somatic cell hybrid analysis, human GluR-7 was localizedmore » to chromosome 1. Fine mapping analysis using FISH localized the gene to 1p33-34. Since glutamate receptors of the kainate subtype have been implicated in neurodegenerative disorders, establishing the precise map position of human GluR-7 subunit is an important step towards evaluating this locus as a candidate for mutations in neurodegenerative disorders.« less
  • The effect of temperature on the binding of ({sup 3}H)-N-(1-(2-thienyl)cyclohexyl)piperidine (({sup 3}H)TCP) to the ion channel of the N-methyl-D-aspartate (NMDA) receptors was studied in washed rat brain-cortex membranes. Raising the temperature from 5 to 33{degree}C resulted in a significant increase in the association rates of ({sup 3}H)TCP binding measured in the presence of 1 {mu}M glutamate and 1 {mu}M glycine, but was less effective in the absence of the added agonists. No such effects of temperature on the dissociation rates of ({sup 3}H)TCP-receptor complexes were observed. In the absence of agonists, neither the association nor the dissociation binding components variedmore » with temperature, suggesting a diffusion-controlled limitation of access of the ligand to its site within the nonactivated NMDA receptor. No evidence was found for a temperature-dependent change in the density of ({sup 3}H)TCP binding sites or for heterogeneity of ({sup 3}H)TCP binding sites associated with the NMDA receptor, even though when approaching equilibrium the binding kinetics in the presence of glutamate and glycine deviated from an ordinary bimolecular reaction scheme. The data were fitted instead to a two-exponent binding function, comprising the sum of a fast and a slow binding component. The results suggest homogeneity of ({sup 3}H)TCP-binding domains within the NMDA receptor channel but variability of total channel opening time. The observed effects of glutamate and of glycine on the kinetic components are consistent with this suggestion.« less
  • GABA[sub A] receptors are hetero-oligomeric ion-channel complexes that are composed of combinations of [alpha], [beta], [gamma], and [delta] subunits and play a major role in inhibitory neurotransmission in the mammalian brain. The authors report here a microsatellite polymorphism within the human [alpha][sub 6]-subunit gene (GABRA6). Mapping of this marker in a human-hamster hybrid cell-line panel and typing of the repeat in the Centre d'Etude du Polymorphisme Humain (CEPH) reference families enabled the localization of this gene to chromosome 5q and established its linkage to the GABA[sub A] receptor [alpha][sub 1]-subunit gene (GA-BRA1) with a maximum lod score (Z[sub max]) ofmore » 39.87 at a [theta] of 0.069 (males) and 0.100 (females). These results reveal the clustering of GABRA6, GABRA1, and the GABA[sub A] receptor [gamma][sub 2]-subunit gene (GABRG2) on distal chromosome 5q. 17 refs., 1 fig., 1 tab.« less
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