Enzyme Translocation In Schizophrenia Pathogenesis
The implication of t(1;11) chromosome translocation in Schizophrenia pathogenesis
Schizophrenia is a severe mental illness that affects approximately 1% of the adult population.1 Due to its complexity, there are many contributions to the genesis of the disease including epigenetic, stochastic and environmental factors, yet studies on families and twins have proved that the genetic component plays a crucial role.2 Multiple Schizophrenia-associated loci have been identified, many of them, revealing little about its mechanisms. In contrast, Disrupted in Schizophrenia 1 (DISC1) represents a particular case. The dysregulation of this gene is caused by the t(1;11) chromosome translocation and although very rare, this mutation shows high correlation …show more content…
This would determine the expression of a shorter protein.10 Moreover, the mRNA containing the premature stop codon was targeted by the nonsense mediated decay pathway which functions to decrease the expression of a potentially harmful truncated protein. Although this mechanism is hypothetical, it has been demonstrated that in cells derived from t(1;11) carriers DISC1 expression is reduced at both mRNA as well as translation level which supports the haploinsufficiency …show more content…
The expression of DB7 fusion gene was also found to decrease rRNA synthesis and general protein translation in both cell studies and in transgenic DISC1-Boymaw mice.5 In mice this was suggested by a reduction in the cellular levels of Gad67, Nmdar1 and Psd95 proteins, in spite of normal levels of mRNA transcripts for the corresponding genes.5 Optimal translation is necessary for neural plasticity and in fact, hypermethylation of rRNA gene promoter has been associated with suicide, cognitive impairment and Alzheimer's disease.11,5 Given that rRNA synthesis is a factor that determines ribosome biogenesis, low levels of rRNA will decrease protein translation as well.5 In addition, the transgenic mice also showed enlarged ventricles, reduced cerebral cortex and thinning of neuronal layers, symptoms that are very common to Schizophrenic
Schizophrenia is a severe mental illness that affects approximately 1% of the adult population.1 Due to its complexity, there are many contributions to the genesis of the disease including epigenetic, stochastic and environmental factors, yet studies on families and twins have proved that the genetic component plays a crucial role.2 Multiple Schizophrenia-associated loci have been identified, many of them, revealing little about its mechanisms. In contrast, Disrupted in Schizophrenia 1 (DISC1) represents a particular case. The dysregulation of this gene is caused by the t(1;11) chromosome translocation and although very rare, this mutation shows high correlation …show more content…
This would determine the expression of a shorter protein.10 Moreover, the mRNA containing the premature stop codon was targeted by the nonsense mediated decay pathway which functions to decrease the expression of a potentially harmful truncated protein. Although this mechanism is hypothetical, it has been demonstrated that in cells derived from t(1;11) carriers DISC1 expression is reduced at both mRNA as well as translation level which supports the haploinsufficiency …show more content…
The expression of DB7 fusion gene was also found to decrease rRNA synthesis and general protein translation in both cell studies and in transgenic DISC1-Boymaw mice.5 In mice this was suggested by a reduction in the cellular levels of Gad67, Nmdar1 and Psd95 proteins, in spite of normal levels of mRNA transcripts for the corresponding genes.5 Optimal translation is necessary for neural plasticity and in fact, hypermethylation of rRNA gene promoter has been associated with suicide, cognitive impairment and Alzheimer's disease.11,5 Given that rRNA synthesis is a factor that determines ribosome biogenesis, low levels of rRNA will decrease protein translation as well.5 In addition, the transgenic mice also showed enlarged ventricles, reduced cerebral cortex and thinning of neuronal layers, symptoms that are very common to Schizophrenic