Research on DNA methylation for two-generation pairs with schizophrenia (Anticipation and modulation of gene expression in schizophrenia)

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The aim of this study was to explore the molecular mechanisms including epigenetic DNA modification underlying genetic anticipation in schizophrenia. Twelve two-generation pairs with schizophrenia, which showed prominent anticipation., were examined.First, we investigated whether the promoter region of dopamine D2 receptor gene (DRD2) was methylated or not, using the methylation-sensitive restriction enzyme, Hap II, and the methylation-insensitive enzyme, MspI. After enzyme digestion, polymerase chain reaction (PCR) was performed, and. the. size of PCR products was determined with polyacrylamide gel electrophoresis. No difference was found between two generation in methylation of the promoter region of DRD2.Second, we measured 5-methyl-2'-deoxycytidine (mC) contents by high performance liquid chromatography (HPLC) in peripheral leukocytes DNA obtained from eight two-generation pairs with schizophrenia, to compare the global methylation levels between two generation. We obtained no significant results in this method.In summary, we found no evidence for the relationship between genetic anticipation and DNA methylation in schizophrenia. Therefore in future studies we will aim to collect more subjects and try other enzymes.