| Project/Area Number |
13307027
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Psychiatric science
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| Research Institution | Mie University |
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Principal Investigator |
OKAZAKI Yuji Mie University, Faculty of Medicine, Professor, 医学部, 教授 (40010318)
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| Co-Investigator(Kenkyū-buntansha) |
YAMASHITA Hideji Kyushu Tokai University, School of Agriculture, Assistant Professor, 農学部, 講師 (20289630)
IMAMURA Akira Nagasaki University, Graduate School of Medicine, Dentist & Pharmacy, Assistant Professor, 大学院・医歯薬学総合研究科, 講師 (40325642)
JINNO Yoshihiro Ryuukyu University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (20179097)
KATO Tadafumi RIKEN Brain Science Institute, Laboratory for Molecular Dynamics of Mental Disorders, Team leader, 精神疾患動態研究チーム, チームリーダー (30214381)
SASAKI Tsukasa University of Tokyo, Health Service Center, Associate Professor, 保健管理センター, 助教授 (50235256)
辻田 高宏 長崎大学, 医学部, 講師 (40304919)
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| Project Period (FY) |
2001 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥52,000,000 (Direct Cost: ¥40,000,000、Indirect Cost: ¥12,000,000)
Fiscal Year 2003: ¥9,230,000 (Direct Cost: ¥7,100,000、Indirect Cost: ¥2,130,000)
Fiscal Year 2002: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Fiscal Year 2001: ¥26,650,000 (Direct Cost: ¥20,500,000、Indirect Cost: ¥6,150,000)
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| Keywords | Mental Diseases / Methylation / Monozygotic twin discordant for a disease / Scizophrenia / Bipolar disorder / XBP1 / Autism / Methylated cytosine / メチル化 / 組織特異性 / FRGP / ゲノム差異 / 遺伝子発現 / 一卵性双生児 / 成因 / エピジェネティックス / メチレーション / ゲノム解析 |
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| Research Abstract |
(1) Methylation and schizophrenia
Total me ethylated cytosine volumes in leucocytes were measured using HPLC and compared between patients with schizophrenia and age and sex matched normal controls. Leucocytes from male patients with schizophrenia contained significantly less total me ethylated cytosine than those from normal controls. The difference was observed especially in the young patients (<35 years old). There was no significant difference for female patients. Two Human endogenous retrovirus (HERV) that retain the transcriptional activity which is inhibited by methylation were located on chromosome 1q21-q22 and 22q12 which were susceptible loci repeatedly observed in the linkage study of schizophrenia. These suggest the involvement of methylation in the pathogenesis of schizophrenia
(2) Differential genomic scans of discordant monozygotic twins
Fluorescent representational genomic profiling (FRGP) was applied to DNAs from monozygotic twins discordant for schizophrenia, bipolar disorder, autism and narcolepsy. Discordant spots containing discordant DNA fragments between affected and non-affected twins from the monozygotic twins from autism, schizophrenia and bipolar disorder. Two candidate genes (4p14, 12q24.11) for autism, 1gnee (6q13) and 1 gene (7q31) were implicated by the direct cloning of the spots. Furthermore, the difference of an autism gene was revealed due to its different methylation status in the promoter region.
(3) The discovery of bipolar disorder susceptibility gene, XBP1
DNA Microarray analysis of lymphoblasted cells from two monozygotic twins discordant for bipolar disorder revealed lower expression of XBP1 and GRP78 genes that involved in the lowered endoplasmic reticulum (ER) stress. A polymorphism (-116 G/C) in the promoter region of XBP1 was responsible for lowered expression. The involvement of methylation in the expression of XBP1 is a next focus
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