| Project/Area Number |
17K17806
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pathological medical chemistry
Medical genome science
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| Research Institution | Nagoya University |
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Principal Investigator |
JIA Nan 名古屋大学, 環境医学研究所, 特任助教 (90754060)
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
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| Keywords | Cockayne syndrome / UV-sensitive syndrome / RNA polymerase II / DDR-deficient disorders / Cockyane Syndrome / 分子遺伝子診断学 / 遺伝子診断 / ゲノム不安定性疾患 / DNA損傷修復 |
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| Outline of Final Research Achievements |
DNA damage and repair (DDR) system is important for maintenance of genome integrity; defects in DDR can result in several genetic disorders. In current research, we finished diagnosis of 124 patients with Cockyane Syndrome (CS), and identified 71 novel pathogenic mutations in the CSA and CSB genes (J Med Genet, 55 (5): jmedgenet-2017-104877, 2018). We considerably broaden the CSA and CSB mutation spectrum responsible for CS, and improves the definition of the puzzling genotype-phenotype relationships in patients with CS.
We also identified several mild cases with R77* mutations in the CSB gene (CS-IV patients) to search for the reason why different mutations in the CSB genes lead to diverse phenotypes. In our research we performed a series of functional analysis with samples deviated from mild CS-IV and severe CS-I / II patients, to explain the distinct severity of CS clinical phenotype.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究により、これまで明らかになっていなかった、コケイン症候群関連疾患の病態の重篤度の違いを引き起こす原因が明らかになると期待される。また、これらの成果を検討することで、コケイン症候群の発症メカニズムの理解や、TCRでのCSBの機能の解明にも貢献するほか、CSB蛋白質との相互作用因子を調査する過程で、新規TCR関連因子を同定できる可能性も含んでいる。以上のことから、申請者の計画研究は、医学的にも、科学的にも重要な研究と考えられる。。
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