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研究生: 謝文昊
Hsieh, Wen-Hao
論文名稱: GR多肽與其上游C9ORF72基因的動態交互作用
Dynamic Interactions between Poly-GR Peptide and its Upstream C9ORF72 Gene
指導教授: 李以仁
Lee, I-Ren
學位類別: 碩士
Master
系所名稱: 化學系
Department of Chemistry
論文出版年: 2019
畢業學年度: 107
語文別: 中文
論文頁數: 67
中文關鍵詞: 肌萎縮性脊髓側索硬化症額顳葉失智症C9ORF72六核苷酸重複序列擴張單分子螢光共振能量轉移二肽重複蛋白
英文關鍵詞: ALS, FTD, C9ORF72, hexanucleotide repeat expansions, smFRET, DPR proteins
DOI URL: http://doi.org/10.6345/NTNU201900426
論文種類: 學術論文
相關次數: 點閱:60下載:0
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  • 謝誌 i 摘要 ii Abstract iii 目錄 iv 圖目錄 vi 表目錄 viii 第一章、緒論 1 1. 1 C9ORF72 (Chromosome 9 open reading frame 72) 與肌萎縮性脊髓側索硬化症及額顳葉失智症關連性 1 1. 2核苷酸序列的重複擴張與衍生疾病 3 1. 2. 1 核苷酸重複序列與其相關疾病介紹 3 1. 2. 2 核甘酸序列擴張機制與二級結構關係 3 1. 3 C9ORF72致病機制 5 1. 3. 1 C9-ALS / FTD致病成因 5 1. 3. 2 C9ORF72產生雙肽蛋白與聚集 6 1. 3. 3蛋白質聚集的形成與神經疾病 8 1. 4 (G4C2)n重複序列與poly—GR交互作用研究 9 第二章、實驗方法與儀器 10 2. 1 實驗儀器與原理 10 2. 1. 1 單分子實驗技術 10 2. 1. 2 單分子螢光共振能量轉移 11 2. 1. 3 全內反射螢光顯微鏡 15 2. 2 實驗器材與樣品置備 17 2. 2. 1 玻片前處理 17 2. 2. 2 DNA的設計 20 2. 2. 3 螢光染料的標記 22 2. 2. 4 DNA黏合反應 23 2. 2. 5 顯像緩衝溶液 (imaging buffer) 24 2. 2. 6 重複二胜肽溶液配置與保存 28 2. 2. 7 實驗流程 28 2. 3 數據處理與分析 31 第三章、實驗結果與討論 36 3. 1 實驗設計 36 3. 2 d(GGGGCC)n 髮夾構型鑑定 37 3. 3重複二胜肽對d(GGGGCC)4 不同二級結構的影響 38 3. 4 (GR)30 與DNA髮夾結構交互作用的專一性探討 39 3. 5 重複二胜肽長度對DNA髮夾結構的影響 40 3. 6 重複二胜肽濃度控制及動力學分析 40 3. 7 再注入實驗 43 3. 8 單分子動態追蹤 44 第四章、結論與未來展望 63 參考文獻 65

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