Determination of the genomic structure and mutation screening in schizophrenic individuals for five subunits of the N-methyl-D-aspartate glutamate receptor

Williams, Nigel Melville ORCID: https://orcid.org/0000-0003-1177-6931, Bowen, Timothy ORCID: https://orcid.org/0000-0001-6050-0435, Spurlock, Gillian, Norton, Nadine ORCID: https://orcid.org/0000-0002-3848-4288, Williams, Hywel John ORCID: https://orcid.org/0000-0001-7758-0312, Hoogendoorn, Bastiaan ORCID: https://orcid.org/0000-0001-9753-169X, Owen, Michael John ORCID: https://orcid.org/0000-0003-4798-0862 and O'Donovan, Michael Conlon ORCID: https://orcid.org/0000-0001-7073-2379 2002. Determination of the genomic structure and mutation screening in schizophrenic individuals for five subunits of the N-methyl-D-aspartate glutamate receptor. Molecular Psychiatry 7 (5) , pp. 508-514. 10.1038/sj.mp.4001030

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Abstract

The glutamatergic system is the major excitatory neurotransmitter system in the CNS. Glutamate receptors, and in particular N-methyl-D-aspartate (NMDA) receptors, have been proposed as mediators of many common neuropsychiatric phenotypes including cognition, psychosis, and degeneration. We have reconstructed the genomic structure of all five genes encoding NMDA receptors in silico. We screened each for sequence variation and estimated the allele frequencies of all detected SNPs in pooled samples of 184 UK Caucasian schizophrenics and 184 UK Caucasian blood donor controls. Only a single non-synonymous polymorphism was found indicating extreme selection pressure. The rarity of non-synonymous changes suggests that such variants are unlikely to make a common contribution to common phenotypes. We found a further 26 polymorphisms within exonic or adjacent intronic sequences. The minor alleles of most of these have a relatively high frequency (63% above 0.2). These SNPs will therefore be suitable for studying neuropsychiatric phenotypes that are putatively related to NMDA dysfunction. Pooled analysis provided no support for association between any of the GRIN genes and schizophrenia.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG) Neuroscience and Mental Health Research Institute (NMHRI)
Uncontrolled Keywords:	candidate gene; NMDA; polymorphism; glutamate
Publisher:	Nature Publishing Group
ISSN:	1359-4184
Last Modified:	01 Dec 2022 09:49
URI:	https://orca.cardiff.ac.uk/id/eprint/633

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