The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia.
The G-protein coupled metabotropic glutamate receptors (GRMs/mGluRs) have been implicated in the aetiology of schizophrenia as they modulate the NMDA response and that of other neurotransmitters including dopamine and GABA.(1-3) Electrophysiological studies in GRM subtype 5 knockout mice reveal, in one study, a sensorimotor gating deficit characteristic of schizophrenia and in another, a key rôle for this gene in the modulation of hippocampal NMDA-dependent synaptic plasticity. In humans, GRM5 levels are increased in certain pyramidal cell neurons in schizophrenics vs controls.(6) Finally, GRM5 has been mapped to 11q14, neighbouring a translocation that segregates with schizophrenia and related psychoses in a large Scottish family, F23 (MLOD score 6.0). We determined the intron/exon structure of GRM5 and identified a novel intragenic microsatellite. A case-control association study identified a significant difference in allele frequency distribution between schizophrenics and controls (P = 0.04). This is suggestive of involvement of the GRM5 gene in schizophrenia in this population.
Devon
R S
RS
Medical Genetics Section, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
Anderson
S
S
Teague
P W
PW
Muir
W J
WJ
Murray
V
V
Pelosi
A J
AJ
Blackwood
D H
DH
Porteous
D J
DJ
D016022:Case-Control Studies; D005787:Gene Frequency; D015894:Genome, Human; D006801:Humans; D018895:Microsatellite Repeats; D008969:Molecular Sequence Data; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*; D012606:Scotland
C578935:GRM5 protein, human; C578936:Grm5 protein, mouse; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate