deleterious grm1 mutations in schizophrenia有害grm1突变精神分裂症.pdfVIP

Deleterious GRM1 Mutations in Schizophrenia 1. 1. 2 1 1 Mohammed Akli Ayoub , Dora Angelicheva , David Vile , David Chandler , Bharti Morar , Juleen A. 3 4 2,5 1 1 Cavanaugh , Peter M. Visscher , Assen Jablensky , Kevin D. G. Pfleger *, Luba Kalaydjieva * 1 Western Australian Institute for Medical Research/UWA Centre for Medical Research, University of Western Australia, Perth, Australia, 2 Centre for Clinical Research in Neuropsychiatry, The University of Western Australia, Perth, Australia, 3 Research School of Biological Sciences, Australian National University, Canberra, Australia, 4 Queensland Institute for Medical Research, Royal Brisbane Hospital, Brisbane, Australia, 5 School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Perth, Australia Abstract We analysed a phenotypically well-characterised sample of 450 schziophrenia patients and 605 controls for rare non- synonymous single nucleotide polymorphisms (nsSNPs) in the GRM1 gene, their functional effects and family segregation. GRM1 encodes the metabotropic glutamate receptor 1 (mGluR1), whose documented role as a modulator of neuronal signalling and synaptic plasticity makes it a plausible schizophrenia candidate. In a recent study, this gene was shown to harbour a cluster of deleterious nsSNPs within a functionally important domain of the receptor, in patients with schizophrenia and bipolar disorder. Our Sanger sequencing of the GRM1 coding regions detected equal numbers of nsSNPs in case