Study of genotype-phenotype correlation and drug development by functional characterization for pendrin variant
| Project/Area Number |
18K16869
|
|---|
| Research Category |
Grant-in-Aid for Early-Career Scientists
|
| Allocation Type | Multi-year Fund |
|---|
| Review Section |
Basic Section 56050:Otorhinolaryngology-related
|
|---|
| 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) |
|---|
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)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2019: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
|
|---|
| Keywords | 遺伝性難聴 / バリアント / VUS / ハイスループット / 遺伝子バリアント / 機能解析 / スプライシング / タンパク機能解析 / ペンドリン / High-throughput / 薬剤スクリーニング |
|---|
| 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).
|
| 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。
|
Report
(4 results)
Research Products
(23 results)
-
-
-
-
-
[Journal Article] Variants encoding a restricted carboxy-terminal domain of SLC12A2 cause hereditary hearing loss in humans2020
Author(s)
Mutai H, Wasano K, Momozawa Y, Kamatani Y, Miya F, Masuda S, Morimoto N, Nara K, Takahashi S, Tsunoda T, Homma K, Kubo M, Matsunaga T
-
Journal Title
Plos Genet
Volume: 16
Issue: 4
Pages: e1008643-e1008643
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
