DNA Methylation and Human Endogenous Retroviruses Linking Genetic and Environmental Factors in the Pathogenesis of Psychiatric Disorders
Project/Area Number |
15591236
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Research Category |
Grant-in-Aid for Scientific Research (C)
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Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Psychiatric science
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Research Institution | University of the Ryukyus |
Principal Investigator |
JINNO Yoshihiro University of the Ryukyus, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (20179097)
|
Co-Investigator(Kenkyū-buntansha) |
SUGIMOTO Jun University of the Ryukyus, Graduate School of Medicine, Instructor, 大学院・医学研究科, 助手 (10315476)
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Project Period (FY) |
2003 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2003: ¥2,600,000 (Direct Cost: ¥2,600,000)
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Keywords | psychiatric disorders / genetic factors / environmental factors / DNA methylation / human endogenous retroviruses / RNAi |
Research Abstract |
(1)Comprehensive screening of EST database for human endogenous retroviruses(HERVs) with transcriptional potential in the brain and experimental confirmation of their activities Among 4.6-million ESTs, we selected 440 thousands that were prepared from various brain-related tissues and cell lines From the 440-thousand ESTs, we extracted 12 HERV loci that may have transcriptional activities. Finally we identified six out of the 12 HERVs by RT-PCR and subsequent cloning & sequencing analysis. (2)Investigation of an anti-sense RNA effect on nearby genes by HERV-read-through transcripts In a previous study, we identified two HERV loci belonging to HERV-H and HERV-K families. That HERV-H(22q12) was located about 4 kb downstream of the SYN3 gene in the reverse orientation. To investigate an anti-sense RNA effect on SYN3 of the HERV-H read-through product, we constructed three expression vectors containing a genomic sequence from the 3'LTR of the HERV-H to the last exon of SYN3, the same genomic sequence except the last exon being reversed, and no sequence of the exon. Experimental conditions are being examined to obtain the best result. (3)A preliminary study on HERV-K methylation Methylation states of the HERV-K family were examined by Southern blot hybridization using a methylation sensitive enzyme. Materials were peripheral leukocytes, fetal brain, fetal liver, and placenta from three different individuals. Although almost loci were heavily methylated, difference of methylation states was observed between tissues and between individuals. The methylation states were higher in the following order : peripheral leukocytes> brain> liver> placenta. When the difference between individuals was A> B≧C in the placentas, this order was also kept in the livers.,
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Report
(3 results)
Research Products
(8 results)