2023 Fiscal Year Annual Research Report
Evaluating the role of cis-regulatory tandem DNA repeats in human disease and evolution
| Project/Area Number |
21H02460
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| Research Institution | Kyoto University |
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Principal Investigator |
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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| Co-Investigator(Kenkyū-buntansha) |
川路 英哉 公益財団法人東京都医学総合研究所, ゲノム医学研究センター, 副センター長 (20525406)
依馬 正次 滋賀医科大学, 動物生命科学研究センター, 教授 (60359578)
井上 詞貴 京都大学, 高等研究院, 特定准教授 (60525369)
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | ゲノム編集 / ゲノム解析 / DNAリピート / ヒトiPS細胞 |
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| Outline of Annual Research Achievements |
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. 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, which triggers cellular DNA repair and reduces the repeat number to one. We verified the repeat sequence with long-read nanopore technology. Moreover, we developed a new gene editing strategy to control VNTR copy-number reduction, which has never been previously achieved. We used this method to generate iPS cells with VNTRs of various copy numbers for disease modeling. With these novel tools, we have begun to study VNTRs more broadly across the human genome and in non-human primate models.
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| Research Progress Status |
令和5年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
令和5年度が最終年度であるため、記入しない。
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