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

精神分裂症两代人DNA甲基化研究（精神分裂症基因表达的预测和调节）

• 批准号: 13671016
• 负责人: IMAMURA Akira
• 金额: $ 2.24万
• 依托单位: Nagasaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671016/
• 关键词: schizophrenia; anticpation; monozygotic twin; DNA methylation; methylation-sensitive restriction enzyme; HPLC; 精神分裂病(統合失調症); 遺伝子発現調整; RLGS法; M-PCR法; 精神分裂病

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.

这项研究的目的是探索精神分裂症中基础遗传预期的分子机制。研究了十二二代与精神分裂症，这表现出了显着的预期。首先，我们研究了多巴胺D2受体基因（DRD2）的启动子区域是否使用甲基化敏感的限制酶，HAP II，HAP II，HAPINALITY-MEXYLATION-INSINLITACH-INSISPINS ANSYLATION-MINSISPINSINS ANSYZEMENZEME，MMSPI，msspi，msspi，msspi。酶消化后，进行聚合酶链反应（PCR），并进行。这。用聚丙烯酰胺凝胶电泳测定PCR产物的大小。在drd2的启动子区域的甲基化中，没有发现差异。我们通过高性能液相色谱法（HPLC）测量了5-甲基-2'-脱氧胞苷（MC）含量（MC）含量，在外周血白细胞中DNA中从八个两代与精神分裂症的两代，与全球甲基化级别进行比较。总而言之，我们没有发现精神分裂症中遗传预期与DNA甲基化之间关系的证据。因此，在未来的研究中，我们将旨在收集更多主题并尝试其他酶。

项目成果

Matsumoto S., Sasaki T., Imamura A., et al.: "HLA classI distribution in Japanese patients with schizophrenia"Am J Med Genet. 114. 42-45 (2002)

Matsumoto S.、Sasaki T.、Imamura A. 等：“日本精神分裂症患者的 HLA I 类分布”Am J Med Genet。

Imamura A..Tsujita T., Kayashima T., et al.: "Lack of association between the hKCa3 gene and the Japanese schizophrenia patients"Psychiatric Genetics. 11. 227-229 (2001)

Imamura A..Tsujita T.、Kayashima T. 等人：“hKCa3 基因与日本精神分裂症患者之间缺乏关联”精神病遗传学。

The Japanese Schizophrenia Sib-pair Linkage Group (JSSLG): "Initial genome-wide scan for linkage with schizophrenia in the Japanese Schizophrenia Sib-pair Linkage Group (JSSLG) families"Am J Med Genet. 120B. 22-28 (2003)

日本精神分裂症同胞对连锁群 (JSSLG)：“对日本精神分裂症同胞对连锁群 (JSSLG) 家族中与精神分裂症的连锁进行初始全基因组扫描”Am J Med Genet。