| Project/Area Number |
08457466
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Ophthalmology
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| Research Institution | Yokohama City University |
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Principal Investigator |
OHNO Shigeaki School of Medicine, Yokohama City University Professor, 医学部, 教授 (50002382)
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| Co-Investigator(Kenkyū-buntansha) |
NAKAMURA Satoshi School of Medicine, Yokohama City University Assistant Professor, 医学部, 講師 (00237398)
YONEMOTO Junichi School of Medicine, Yokohama City University Assistant Professor, 医学部・附属病院, 講師 (00240383)
SUGITA Miyuki School of Medicine, Yokohama City University Associate Professor, 医学部, 助教授 (90235888)
ITOH Norihiko School of Medicine, Yokohama City University Assistant, 医学部, 助手 (80264654)
UCHIO Eiichi School of Medicine, Yokohama City University Assistant Professor, 医学部・附属病院, 講師 (70232840)
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| Project Period (FY) |
1996 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1997: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1996: ¥4,800,000 (Direct Cost: ¥4,800,000)
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| Keywords | Behcet's desease / Molecular genetics / HLA-BィイD1*ィエD15101 / MICA / MICB / Disease susceptibility gene / HLA-B*5101 / HLA / YACクローン |
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| Research Abstract |
In order to investigate the molecular genetic mechanism of Behcet's disease, we studied the HLA-B region which is located on the short arm of chromosome 6 (6p21.3). A YAC clone, Y109, was isolated from the YAC library using HLA class I specific primers. We investigated the new genes around the HLA-B which are in linkage disequilibrium with HLA-BィイD1*ィエD15101.
Y109 was found to span 600kb. This region was confirmed to contain NOB1, NOB2, NOB3, MICA and MICB, which are non-HLA genes. Investigation of MICB polymorphism by PCR-SSP showed no significant association with Behcet's disease. In contrast, the frequency of MICA-A6 was significantly higher in the patients than in the normal controls.
Furthermore, investigation of amino acids in the peptide binding region of MICA-A6 (exon 3) showed that they were all valine at position 122.
Studies on the other gene regions near the telomere on 6p showed weak association with Behcet's disease, and it was concluded that the responsible gene for Behcet's disease is located in the 230 kb between HLA-C and MICB.
Further studies on the association of Behcet's disease with these new genes are indicated. Establishment of transgenic animals of HLA-BィイD1*ィエD15101-MICA-A6 are now in progress in our laboratory, to elucidate the exact molecular genetic mechanism of this difficult disease.
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