| Project/Area Number |
17590285
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Human genetics
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| Research Institution | University of Tsukuba |
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Principal Investigator |
ARINAMI Tadao University of Tsukuba, Graduate School of Comprehensive Human Sciences, Professor, 大学院人間総合科学研究科, 教授 (10212648)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2005: ¥2,900,000 (Direct Cost: ¥2,900,000)
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| Keywords | Schizophrenia / Methylation / Genome / Brain / RNA / Gene expression / Methyl-CpG binding protein / Glutamate receptors / アイソフォーム |
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| Research Abstract |
Schizophrenia is a highly heritable disorder with over 70% of heritability. However, in addition to genetic backgrounds, epigenetic influence is thought to play a great role in developing schizophrenia. DNA methylation is one of the epigenetic mechanisms and plays a critical role in gene expression. In the present study project, we tried to find out the down-regulated genes in schizophrenia brains by performing DNA methylation screening of CpG islands located in coding regions.
DNA samples from patients and controls were digested into fragments, and the methylated DNA fragments were collected by in vitro selection method. A subtraction technique was performed in order to remove common methylated DNA fragments between both groups. The candidate genes were selected by hybridization of subtracted DNA fragments to cDNA chips.
Expression levels of selected candidate genes were evaluated by TaqMan real-time PCR gene expression analyses in RNAs, from prefrontal cortex of schizophrenia patients and controls. We also searched different levels of gene expression in both patients and controls in the Stanley Medical Research Institute Online Genomics Database.
The state of DNA methylation in candidate genes was detected by bisulfite-cloning and sequencing.
We identified 25 hyper-methylated genes in schizophrenia brains compared with those in control brains. 10 genes were expressed lower and 5 gene were expressed higher in schizophrenics prefrontal cortex. In a single patient, one of these genes was methylated higher in the prefrontal cortex than in its control. The methods used in the present study are useful for screening differentially methylated genomic regions, that has an influence in gene expression levels. The findings of the present study may prove the significant role of epigenetic mechanisms in schizophrenia.
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