| 研究課題/領域番号 |
23KF0041
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| 研究種目 |
特別研究員奨励費
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| 配分区分 | 基金 |
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| 応募区分 | 外国 |
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| 審査区分 |
小区分43050:ゲノム生物学関連
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| 研究機関 | 京都大学 |
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研究代表者 |
ウォルツェン クヌート 京都大学, iPS細胞研究所, 准教授 (50589489)
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| 研究分担者 |
MARTINEZ GALVEZ GABRIEL 京都大学, iPS細胞研究所, 外国人特別研究員
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| 研究期間 (年度) |
2023-04-25 – 2024-03-31
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| 研究課題ステータス |
完了 (2023年度)
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| 配分額 *注記 |
1,500千円 (直接経費: 1,500千円)
2023年度: 1,500千円 (直接経費: 1,500千円)
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| キーワード | DNAリピート / ゲノム編集 / CRISPR-Cas9 / iPS細胞 / レポーターアッセイ |
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| 研究開始時の研究の概要 |
Tandem repeat copy-number variations have been correlated with changes in gene expression and are probable causes of human disease. We are developing gene editing and computational biology methods to efficiently generate repeat-variant disease models in human induced pluripotent stem (iPS) cells. Moreover, we are developing technologies to produce intermediate copy-number variants. As proof-of-concept, we completed the generation of a repeat-copy variants in iPS cells at two loci with known clinically relevance, and aim to apply these methods genome-wide.
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| 研究実績の概要 |
Variable Number Tandem Repeats (VNTRs) are repetitive DNA sequences that differ in number between individuals. VNTR copy number is shown to correlate with changes in gene expression, and are probable causes of human disease. To understand these relationships, we developed a new bioinformatic pipeline to identify, analyze, and design gene editing strategies for VNTRs, which has never been previously achieved. We characterized 5 VNTRs for copy-number polymorphisms across 22 human iPS cell lines. We designed CRISPR-Cas9 strategies that target and cut each repeats, triggering cellular DNA repair that reduces the repeat number to one. Moreover, we developed a novel gene editing strategy to control VNTR copy-number to generate iPS cells with VNTRs of various copy numbers for disease modeling.
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