2023 Fiscal Year Annual Research Report
ゲノム編集を駆使したシスエレメントの反復配列多型による遺伝子発現制御の理解
| Project/Area Number |
23KF0041
|
|---|
| Research Institution | Kyoto University |
|---|
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)
|
|---|
| 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
|
|---|
| Project Period (FY) |
2023-04-25 – 2024-03-31
|
| Keywords | DNAリピート / ゲノム編集 / CRISPR-Cas9 / iPS細胞 / レポーターアッセイ |
|---|
| 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, 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.
|
