Identification and Molecular Analysis of a Potential Disease-causing Mutation in gene A in Congenital Radioulnar Synostosis
| Project/Area Number |
16K10852
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Orthopaedic surgery
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| Research Institution | Shinshu University |
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Principal Investigator |
Kato Hiroyuki 信州大学, 学術研究院医学系, 教授 (40204490)
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| Co-Investigator(Kenkyū-buntansha) |
中村 幸男 信州大学, 学術研究院医学系(医学部附属病院), 講師 (00549488)
林 正徳 信州大学, 学術研究院医学系, 助教 (20624703)
岩崎 倫政 北海道大学, 医学研究院, 教授 (30322803)
小松 雅俊 信州大学, 医学部附属病院, 特任研究員 (60723070)
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| Research Collaborator |
Suzuki Takako
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 遺伝子 / 先天性橈尺骨癒合症 / 全エクソン解析 |
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| Outline of Final Research Achievements |
Congenital radioulnar synostosis is a skeletal disorder resulting in fusion of the radius and ulna. Since the etiology is largely unknown, elucidation of pathophysiology of RUS is needed for development of better treatment.
We collected DNA samples of 10 trios (an affected patient and his or her biological parents) and performed whole exome-sequencing (WES). We identified mutations in several candidate genes including the gene A. The WES identified the following potential disease-causing de novo heterozygous missense mutation in a patient. We performed whole-mount in situ hybridization (ISH) in zebrafish. ISH showed specific expression of gene A in pectoral fins, which correspond to human upper limbs, and in craniofacial regions. Gene A knockdown in zebrafish caused defects in pectoral fins and dorso-ventral patterning, which are likely caused by inhibitory effects of bone morphogenetic protein (BMP) action. These abnormalities were partially rescued by bmp2b RNA overexpression.
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| Academic Significance and Societal Importance of the Research Achievements |
本事業により、先天性橈尺骨癒合症の原因遺伝子同定とその遺伝子の機能が明らかになる。また遺伝子を標的とした発症抑制のオーダーメイド治療法の開発の糸口となる。
手術を行う整形外科医が臨床の視点に立って遺伝子解析を行う事は、基礎医学から臨床応用の発展に繋がる。さらに本研究は、関節の発生、分化における遺伝子発現の知見が得られ、骨関節の再生医療に役立つと考えられる。
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Report
(4 results)
Research Products
(1 results)
