Genetic analysis of the DLGAP1 gene as a candidate gene for schizophrenia

Abstract: Schizophrenia is a severe chronic mental disorder with high genetic components in its etiology. Several studies indicated that synaptic dysfunction is involved in the pathophysiology of schizophrenia. Postsynaptic synapse-associated protein 90/postsynaptic density 95-associated proteins (SAPAPs) constitute a part of the N-methyl-d-aspartate receptor-associated postsynaptic density proteins, and are involved in synapse formation. We hypothesized that genetic variants of the SAPAPs might be associated with schizophrenia. Thus, we systemically sequenced all the exons of the discs, large (Drosophila) homolog-associated protein 1 (DLGAP1) gene that encodes SAPAP1 in a sample of 121 schizophrenic patients and 120 controls from Taiwan. We totally identified six genetic variants, including five known SNPs (rs145691437, rs3786431, rs201567254, rs3745051 and rs11662259) and one rare missense mutation (c.1922A>G) in this sample. SNP- and haplotype-based analyses showed no association of these SNPs with schizophrenia. The c.1922A>G mutation that changes the amino acid lysine to arginine at codon 641 was found in one out of 121 patients, but not in 275 control subjects, suggesting it might be a patient-specific mutation. Nevertheless, bioinformatic analysis showed this mutation does not affect the function of the DLGAP1 gene and appears to be a benign variant. Hence, its relationship with the pathogenesis remains to be investigated. [Copyright &y& Elsevier]