Identification of single nucleotide polymorphisms (SNPs) and other sequence changes and estimation of nucleotide diversity in coding and flanking regions of the NMDAR1 receptor gene in schizophrenic patients

Molecular Psychiatry
S R RiceJ L Sobell

Abstract

Glutamatergic dysregulation has been hypothesized to play a role in schizophrenia. The N-methyl-D-aspartate (NMDA) type of glutamate receptor especially is of interest because, in addition to binding sites for glutamate and glycine, a necessary co-agonist, this receptor also contains noncompetitive binding sites for the psychotomimetics phencyclidine (PCP), MK-801, and ketamine. PCP-induced psychosis has been a useful disease model in that both the positive as well as the negative symptomatologies seen in schizophrenia are observed. Recently, a mouse deficient in expression of the NR1 subunit gene (NMDAR1) of the heteromeric receptor has been developed and shown to display aberrant behaviors, with reduced social and sexual interactions as well as increased stereotypic motor activity. In an extensive examination of the NMDAR1 gene in our laboratory in approximately 100 chronic schizophrenic patients, 28 unique sequence changes were identified, including eight single nucleotide polymorphisms (SNPs) in the 5' untranslated region (5'UTR), six SNPs in coding regions (cSNPs), eleven intronic SNPs, two intronic deletions of 7 and 30 bp, and an intronic microinsertion/deletion. With the exception of one previously reported cSNP, all of...Continue Reading

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Citations

Sep 17, 2008·Journal of Molecular Neuroscience : MN·Hamid GalehdariMostafa Saadat
Dec 13, 2006·Development and Psychopathology·Angus W MacDonald, Matthew V Chafee
Aug 11, 2007·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Yukihiro NodaAkihiro Mouri
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Feb 3, 2004·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·N NiuJ L Sobell
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Aug 17, 2019·Frontiers in Molecular Neuroscience·Gloria Lee, Yi Zhou

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