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The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia

Molecular Psychiatry volume 6, pages 311–314 (2001)Cite this article

Abstract

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 schizophrenia4 and in another, a key rôle for this gene in the modulation of hippocampal NMDA-dependent synaptic plasticity.5 In humans, GRM5 levels are increased in certain pyramidal cell neurons in schizophrenics vscontrols.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).7,8 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.

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References

  1. Olney JW, Farber NB . Glutamate receptor dysfunction and schizophrenia Arch Gen Psychiatry 1995 52: 998–1007

    Article  CAS  PubMed  Google Scholar 

  2. Mohn AR, Gainetdinov RR, Caron MG, Koller BH . Mice with reduced NMDA receptor expression display behaviors related to schizophrenia Cell 1999 98: 427–436

    Article  CAS  PubMed  Google Scholar 

  3. Bordi F, Ugolini A . Group I metabotropic glutamate receptors: implications for brain diseases Prog Neurobiol 1999 59: 55–79

    Article  CAS  PubMed  Google Scholar 

  4. Geyer MA, Dulawa SC, Ralph RJ, Henry SA . Startle habituation and prepulse inhibition studies in mutant mice 55th Annual Conference of the Society of Biological Psychiatry, USA April 2000

  5. Lu YM, Jia Z, Janus C, Henderson JT, Gerlai R, Wojtowicz JM et al. Mice lacking metabotropic glutamate receptor 5 show impaired learning and reduced CA1 long-term potentiation (LTP) but normal CA3 LTP J Neurosci 1997 17: 5196–5205

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Ohnuma T, Augood SJ, Arai H, McKenna PJ, Emson PC . Expression of the human excitatory amino acid transporter 2 and metabotropic glutamate receptors 3 and 5 in the prefrontal cortex from normal individuals and patients with schizophrenia Brain Res Mol Brain Res 1998 56: 207–217

    Article  CAS  PubMed  Google Scholar 

  7. St Clair D, Blackwood D, Muir W, Carothers A, Walker M, Spowart G et al. Association within a family of a balanced autosomal translocation with major mental illness Lancet 1990 336: 13–16

    Article  CAS  PubMed  Google Scholar 

  8. Blackwood D, Fordyce A, Walker M, StClair D, Porteous D, Muir W . Thirty-year follow-up of a family showing association of schizophrenia with a balanced translocation t(1:11)(q42,q14.3) Am J Med Genet 1998 81: 532

    Google Scholar 

  9. Devon RS, Porteous DJ . Physical mapping of a glutamate receptor gene in relation to a balanced translocation associated with schizophrenia in a large Scottish family Psychiatr Genet 1997 7: 165–169.

    Article  CAS  PubMed  Google Scholar 

  10. Devon RS, Evans KL, Maule JC, Christie S, Anderson S, Brown J et al. Novel transcribed sequences neighbouring a translocation breakpoint associated with schizophrenia Am J Med Genet 1997 74: 82–90

    Article  CAS  PubMed  Google Scholar 

  11. Millar JK, Brown J, Maule JC, Shibasaki Y, Christie S, Lawson D et al. A long-range restriction map across 3 Mb of the chromosome 11 breakpoint region of a translocation linked to schizophrenia: localization of the breakpoint and the search for neighbouring genes Psychiatr Genet 1998 8: 175–181

    Article  CAS  PubMed  Google Scholar 

  12. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W et al. Gapped BLAST and PSI-BLAST: a new generation of protein database search programs Nucl Acids Res 1997 25: 3389–3402

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Daggett LP, Sacaan AI, Akong M, Rao SP, Hess SD, Liaw C et al. Molecular and functional characterization of recombinant human metabotropic glutamate receptor subtype 5 Neuropharmacology 1995 34: 871–886

    Article  CAS  PubMed  Google Scholar 

  14. Underhill PA, Jin L, Lin AA, Mehdi SQ, Jenkins T, Vollrath D et al. Detection of numerous Y chromosome biallelic polymorphisms by denaturing high-performance liquid chromatography Genome Res 1997 7: 996–1005

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. O'Donovan MC, Oefner PJ, Roberts SC, Austin J, Hoogendoorn B, Guy C et al. Blind analysis of denaturing high-performance liquid chromatography as a tool for mutation detection Genomics 1998 52: 44–49

    Article  CAS  PubMed  Google Scholar 

  16. Smit AFA, Green P . RepeatMasker. URL: http://ftp.genome. washington.edu/RM/RepeatMasker.html

  17. Cochrane WG . Some methods for strengthening the common chi-squared test Biometrics 1954 10: 417–451

    Article  Google Scholar 

  18. Shaw SH, Kelly M, Smith AB, Shields G, Hopkins PJ, Loftus J et al. A genome-wide search for schizophrenia susceptibility genes Am J Med Genet 1998 81: 364–376

    Article  CAS  PubMed  Google Scholar 

  19. Coon H, Jensen S, Hoff M, Holik J, Plaetke R, Reimherr F et al. A genome-wide search for genes predisposing to manic-depression, assuming autosomal dominant inheritance Am J Hum Genet 1993 52: 1234–1249

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Levinson DF, Mahtani MM, Nancarrow DJ, Brown DM, Kruglyak L, Kirby A et al. Genome scan of schizophrenia Am J Psychiatry 1998 155: 741–750

    CAS  PubMed  Google Scholar 

  21. Maziade M, Raymond V, Cliche D, Fournier JP, Caron C, Garneau Y et al. Linkage results on 11Q21-22 in Eastern Quebec pedigrees densely affected by schizophrenia Am J Med Genet 1995 60: 522–528

    Article  CAS  PubMed  Google Scholar 

  22. Wang ZW, Black D, Andreasen NC, Crowe RR . A linkage study of chromosome 11q in schizophrenia Arch Gen Psychiatry 1993 50: 212–216

    Article  CAS  PubMed  Google Scholar 

  23. Ewald H, Mors O, Flint T, Friedrich U, Eiberg H, Kruse TA . Linkage analysis between manicdepressive illness and markers on the long arm of chromosome 11 Am J Med Genet 1995 60: 386–392

    Article  CAS  PubMed  Google Scholar 

  24. Endicott J, Spitzer RL . A diagnostic interview: the schedule for affective disorders and schizophrenia Arch Gen Psychiatry 1978 35: 837–844

    Article  CAS  PubMed  Google Scholar 

  25. McGuffin P, Farmer AE, Harvey IH . A polydiagnostic application of operational criteria in studies of psychotic illness: development and reliability of the OPCRIT system Arch Gen Psychiatry 1991 48: 764–770

    Article  CAS  PubMed  Google Scholar 

  26. Huber CG, Oefner PJ, Bonn GK . High resolution liquid chromatography of oligonucleotides on nonporous alkylated styrene-divinylbenzene copolymers Anal Chem 1993 67: 578–585

    Article  Google Scholar 

  27. Ewing B, Hillier L, Wendl M, Green P . Basecalling of automated sequencer traces using phred. I. Accuracy assessment Genome Res 1998 8: 175–185

    Article  CAS  PubMed  Google Scholar 

  28. Ewing B, Green P . Basecalling of automated sequencer traces using phred. II. Error probabilities Genome Res 1998 8: 186–194

    Article  CAS  PubMed  Google Scholar 

  29. Gordon D, Abajian C, Green P . Consed: a graphical tool for sequence finishing Genome Res 1998 8: 195–202

    Article  CAS  PubMed  Google Scholar 

  30. Minakami R, Katsuki F, Sugiyama H . A variant of metabotropic glutamate receptor subtype 5: an evolutionally conserved insertion with no termination codon Biochem Biophys Res Commun 1993 194: 622–627

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We would like to thank Martin Taylor and Stephanie Le Hellard for their assistance with bioinformatics, Maura Walker for collating patient data and Dr Peng Lee Yap for his generous assistance in providing blood samples. This work was supported by the UK Medical Research Council and Organon Laboratories, Newhouse, Lanarkshire, UK. VM is funded by the John, Margaret, Alfred and Stewart Sim Fellowship through The Royal College of Physicians of Edinburgh.

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Author notes

  1. R S Devon

    Present address: Centre for Molecular Medicine and Therapeutics, 980 West 28th Avenue, Vancouver, V5Z 4H4, BC, Canada

Authors and Affiliations

  1. Medical Genetics Section, University of Edinburgh, Molecular Medicine Centre, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK

    R S Devon, S Anderson & D J Porteous

  2. MRC Human Genetics Unit, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK

    P W Teague

  3. Department of Psychiatry, University of Edinburgh, Royal Edinburgh Hospital, Morningside Park, Edinburgh, EH10 5HF, UK

    W J Muir & D H R Blackwood

  4. Department of Adolescent Psychiatry, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G12 0XH, UK

    V Murray

  5. Department of Psychiatry, Hairmyres Hospital, East Kilbride, G75 8RG, UK

    A J Pelosi

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Correspondence to D J Porteous.

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Devon, R., Anderson, S., Teague, P. et al. The genomic organisation of the metabotropic glutamate receptor subtype 5 gene, and its association with schizophrenia. Mol Psychiatry 6, 311–314 (2001). https://doi.org/10.1038/sj.mp.4000848

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