Based on the genetic and functional analysis of the DLG4 gene in the present study, we suggest that subjects carrying the C-D haplotype that is associated with schizophrenia and shows a significant low reporter gene activity may have a reduced expression of PSD95. Similarly, subjects that carry the T allele of the rs13331 that is associated with schizophrenia and shows a low reporter gene activity may also have a decreased level of PSD95. Taken together, the present study suggests reduced DLG4 gene expression may confer increased risk to schizophrenia. PSD95 plays an essential role in the trafficking, clustering, and anchoring of the NMDA receptor at the postsynaptic membrane. Expression of PSD95 selectively enhances NR2A and NR2B expression, which results in increased NR1/NR2A and NR1/ NR2B expression. PSD95 also modulates the channel gating of the NMDA receptor by increasing the channel opening rate. Hence, the reduced PSD95 expression in those subjects carrying the C-D haplotype and the T allele of the rs13331 may lead to a reduction of the functional NMDA receptor or a compromised NMDA receptor-mediated signaling transduction. Furthermore,Nutlin-3 PSD95 forms a big protein complex by interacting directly and indirectly with many synaptic adhesion proteins and intracellular molecules. Hence, the influence of reduced expression of the PSD95 may not be limited to the NMDA receptor. For example, PSD95 is required for activity- driven synapse formation ; PSD95 also interacts with the dopamine D1 receptor and is involved in the reciprocal facilitating, positive feedback loop between the dopamine D1 receptor and NMDA receptor ; PSD95 is also involved in neuroligin-mediated excitatory and inhibitory synapse formation ; PSD95 is reported to regulate dendritic spine growth and synaptic plasticity. Taken together,ONX-0914 reduced expression of PSD95 may have broad and diverse influences on synaptic plasticity and function. The clinical significance and the relevance of these findings to the pathogenesis and pathophysiology of schizophrenia remain to be explored. In summary, we characterized a specific haplotype at the promoter and a SNP at the 39UTR of the DLG4 gene that were associated with increased liability to schizophrenia. These genetic markers may lead to reduced expression of the PSD95 in the brain, and exert broad and diverse influence on the pathogenesis of schizophrenia. However, the study is limited by its small sample size, and the borderline statistical significance. Independent studies with larger sample size are needed to verify the findings from the present study. Biological molecules are subject to random fluctuations in the rates of their synthesis, distribution, activity and decay. This noise becomes more significant as the number of molecules involved becomes small and can potentially interfere with the efficient functioning of gene regulatory networks. GRNs that must make reliable developmental decisions are presumably designed to minimize noise but it is not well understood how this is achieved. Here we examine how noise is reduced in in silico GRNs selected to reliably perform an informed lysis-lysogeny decision like that made by bacteriophage l. A standard approach in in silico biology is to fit parameters to molecular mechanisms in order to reproduce observed features. While this approach often gives useful insights into particular regulatory systems, it only provides a limited understanding of why a given regulatory network has a specific structure. Many models of this type have been used to analyse the developmental decision of the l bistable GRN.