2020 Fiscal Year Final Research Report
Study of genotype-phenotype correlation and drug development by functional characterization for pendrin variant
| Project/Area Number |
18K16869
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 56050:Otorhinolaryngology-related
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| Research Institution | 独立行政法人国立病院機構(東京医療センター臨床研究センター) |
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Principal Investigator |
Wasano Koichiro 独立行政法人国立病院機構(東京医療センター臨床研究センター), 聴覚・平衡覚研究部, 室長 (40528866)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | 遺伝性難聴 |
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| Outline of Final Research Achievements |
We developed an experimental approach to efficiently quantify the pathogenic effects of disease-associated genetic variants with a focus on SLC26A4, which is essential for normal inner ear function. Alterations of this gene are associated with both syndromic and nonsyndromic hereditary hearing loss with various degrees of severity. We established HEK293T-based stable cell lines that express pendrin missense variants in a doxycycline-dependent manner, and systematically determined their anion transport activities with high accuracy in a 96-well plate format using a high throughput plate reader.
Based on the method, we also developed an experimental approach to quantify the function of wild-type and variant of NLCC1(SLC12A2 gene).
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| Free Research Field |
耳鼻咽喉科学、聴覚、難聴遺伝学
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| Academic Significance and Societal Importance of the Research Achievements |
近年の遺伝子解析技術の進歩により多くの遺伝子バリアントが発見されるが、そのバリアントが難聴の原因になのかどうかの判断は非常に難しい場合がある。今回の研究で開発した解析法では効率的にバリアントの機能への影響を定量することが可能であることから、どのバリアントがどのように疾患に関わっているのかを定量化することができる基礎的データを構築することができた。
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