| Project/Area Number |
18K15889
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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 53020:Cardiology-related
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| Research Institution | Osaka University |
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Principal Investigator |
Takuwa Ayako 大阪大学, 免疫学フロンティア研究センター, 特任研究員 (50779791)
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| Project Period (FY) |
2018-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2019: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 遺伝子解析 / 循環器疾患 / スプライシング異常 / スプライシング / 遺伝性循環器疾患 / 血液腫瘍 / RNAseq / 心筋症 |
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| Outline of Final Research Achievements |
In the first half of this study period, mutations causing splicing abnormalities were searched for by combining RNA-seq and WES. We performed WES and RNA-seq on heart transplant patients with inherited cardiovascular disease in whom no known pathogenic mutations were identified. Based on the comparison of their read mapping results, I found multiple candidates splicing aberration-causing mutations.
On the other hand, in the second half of this study period, due to a change in research institutions, my research focus became hematologic tumors, and I attempted to construct a rapid diagnostic system combining WES or targeted DNA sequencing with long-read RNA-seq, focusing on somatic mutations. As a result, pathogenic mutations could be identified in about 30% of the cases analyzed, and the analysis pipeline has been improved resulting in a significant reduction in the number of analysis days.
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| Academic Significance and Societal Importance of the Research Achievements |
希少な遺伝性疾患は単一変異を原因としたものが多く、その病原変異の特定のためには、全エクソーム解析(WES)を含むNGSを用いた網羅的な遺伝子解析が有効である。しかしながら、遺伝子異常が強く疑われる症例であっても、WESでその原因変異を同定できる症例は50%程度にとどまっている。未解決の症例の中には、一見してアミノ酸変異を引き起こす変異はないものの、コピー数異常や構造異常、スプライシング異常を引き起こしているパターンが含まれていると想定されており、その解決は、治療方針の決定や遺伝カウンセリングに役立てることができるほか、高精度のスプライシング異常予測プログラムの開発に向けた情報を提供しうる。
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