| Project/Area Number |
21F21382
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 外国 |
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| Review Section |
Basic Section 43050:Genome biology-related
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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) |
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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| Project Period (FY) |
2021-11-18 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2022: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2021: ¥300,000 (Direct Cost: ¥300,000)
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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 / genome editing / genome analysis / DNA repeat / human iPS cells |
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| Outline of Research at the Start |
Recent advances in DNA sequencing technology have revealed that repetitive regions of DNA are common in the human genome. Repetitive DNA can be found in or near known disease genes. Moreover, repetitive DNA can vary in length amongst individuals. Thus, repetitive DNA has been implicated in influencing human health. This study aims to use genome editing in human induced pluripotent stem cells (iPSCs) to define how repetitive DNA controls disease-gene expression, with the goal of understanding human health and evolution.
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| Outline of Annual Research Achievements |
The project aims to identify variable tandem repeats (VNTRs) at potential regulatory features, like promoters and enhancers, to inform functional analyses in human iPSCs by gene editing. The candidate developed a computational pipeline to detect tandem repeats at candidate enhancer regions (cCREs) on the ENCODE dataset. The candidate also identified VNTRs in the literature which are proposed to be involved in human disease. The project aims to develop gene editing methods to generate variants in healthy iPSCs. The candidate succeeded in editing repeat contractions at two loci in iPSCs: ADGRG1 (reducing two copies to one copy) and TRIB3 (reducing three or five copies to one copy). TRIB3 editing results have been sequenced using Nanopore long-read technology and an analysis pipeline to genotype the editing results is being established. Moreover, the candidate developed a method based on a novel formulation of gene editing reagents which could be used to generate intermediate numbers of DNA repeat variants. These achievements lay the groundwork for a streamlined pipeline for the analysis of the rest of the identified gene editing sites, enabling the subsequent goals of the project.
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| Research Progress Status |
令和4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4年度が最終年度であるため、記入しない。
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