| Project/Area Number |
17K07258
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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 |
Medical genome science
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| Research Institution | Tokyo Women's Medical University |
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Principal Investigator |
Iwasaki Naoko 東京女子医科大学, 医学部, 教授 (70203370)
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2019: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000)
Fiscal Year 2018: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | MODY / 若年発症糖尿病 / 単一遺伝子糖尿病 / 次世代シーケンサー / 個別化医療 / monogenic diabetes / 糖尿病 / 単一遺伝子異常 / 網羅的解析 / targeted sequencing / ゲノム医療 / 原因遺伝子 / 単一遺伝子疾患 / ゲノム / 単一遺伝子病 |
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| Outline of Final Research Achievements |
MODY is a subtype of diabetes mellitus characterized by early age of onset, autosomal dominant mode of inheritance and lack of obesity. MODY is caused by a single gene disorder and a good model for personalized medicine, because of the better autocomes on patients' QOL and overall medical costs. The number of MODY in JAPAN is estimated at least 12,000.
To promote such personalized medicine for MODY in JAPAN, we aimed to clarify the causative gene of Japanese MODY. 61 MODY were comprehensively analyzed with a next-generation sequencer (NGS). Mutations were identified in 16 (26.2%) and possibly pathogenic variants were detected in 8 (13.1%), for a total of 24 (39.3%). Including the SLC308A, INSR, and WFS1 genes, polymorphisms with amino acid substitutions were detected in 26 (42.6%), thus, in total we identified any substitutions in 50 among 61 MODY (81.9%), indicating that NGS is a powerful tool for analyzing MODY causative genes as well as novel susceptible genes.
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| Academic Significance and Societal Importance of the Research Achievements |
61名の規模のMODYの原因遺伝子を明らかにするための、次世代シーケンサーを用いた網羅的検討は知りうる限りではわが国においては我々が最初である。これまで実施してきたサンガー解析、MLPA解析、micro array解析の結果をすべて統合し、MODY約300例の解析結果をまとめて論文化する準備を進めている。
この報告は我が国独自の成績として海外で参照されることが期待され、人種によるMODYの頻度差などの検討に資すると考えられる。さらに我が国において大きく遅れている糖尿病の個別化医療の推進は患者QOLの向上を通じて社会貢献につながるほか、遺伝子解析結果は糖尿病新規治療薬のシーズとして期待される。
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