[Genetic variants of susceptible genes to schizophrenia and their role on disease progress]

ABSTRACT

Schizophrenia is a severe psychiatric disorder that has a lifetime prevalence of 1% in the most studied population. Schizophrenia is a multifactorial disorder that is characterized by the contribution of multiple susceptibility genes that could act in conjunction with epigenetic processes and environmental factors. Linkage and association studies have shown a number of candidate risk genes including Nerugulin 1, Disrupted in schizophrenia, Disbyndin and Epsin 4 that have associated with schizophrenia. However, their biological function remains elusive. 'Disrupted in schizophrenia 1' [DISC1], a gene locus originally identified at the first in a large Scottish family, showing a heavy burden of major mental illnesses associated with a balanced t[1;11][q42.1;q14.3] chromosome translocation. Substantial genetic and biological research on DISC1 has been displayed in past decade that DISC1 is now recognized as a genetic risk factor for a spectrum of psychiatric disorders and it impacts on many aspects of central nervous system [CNS] function, including neurodevelopment, neurosignaling, and synaptic functioning. Evidences emerged from genetic studies have shown a relationship between DISC1 and quantitative traits, including working memory, cognitive aging, gray matter volume in the prefrontal cortex, and abnormalities in hippocampal structures as well as function. DISC1 interacts with numerous proteins, also involved in neuronal migration, neurite outgrowth, cytoskeletal modulation, and signal transduction, some of which have been reported as independent genetic susceptibility factors for psychiatric morbidity. Here, we studied association of genetic variants of several susceptibility genes to schizophrenia, specially DISC1 and its intractor proteins and their effect on functional and structural of the brain in human and in the mouse