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論文中文名稱:利用結合酵素及單磷酸腺苷以定量短縱列重複序列片段數目之研究 [以論文名稱查詢館藏系統]
論文英文名稱:A study of quantification of the copy number of short tandem repeats using ligation and bioluminescence method [以論文名稱查詢館藏系統]
院校名稱:臺北科技大學
學院名稱:工程學院
系所名稱:生物科技研究所
畢業學年度:99
出版年度:100
中文姓名:姚秋好
英文姓名:Chou-Hao Yao
研究生學號:98688022
學位類別:碩士
語文別:中文
口試日期:2011-07-15
論文頁數:71
指導教授中文名:侯劭毅
口試委員中文名:王勝仕;黃志宏;黃光策
中文關鍵詞:短縱列重複序列單磷酸腺苷連結酵素
英文關鍵詞:Short tandem repeatadenosine monophosphateNAD+-dependent ligase
論文中文摘要:短縱列重複序列(short tandem repeat, STR)為一種為廣泛出現在真核生物基因組中大約由1~6個鹼基構成且具有多型性特性的序列,常做為親子鑑定、刑事鑑定及族群分類上的分析工具。
在本研究中偵測短縱列重複序列的重複片段數目,在此利用各種不同片段長度的目標短縱列重複序列為模板,以引子互相黏合後,加入大量與目標序列互補的DNA片段,再利用DNA連結酶將每個片段間進行連結反應。在反應過程中根據模板所具有的短縱列重複序列片段數目,會釋放出相對應數量之單磷酸腺苷。再經由一系列酵素的轉換將單磷酸腺苷轉換成三磷酸腺苷,最後以冷光酶(luciferase)偵測定量之。在10~140nM的濃度範圍,單磷酸線苷其迴歸係數可達0.9998,而利用不同數目片段的短縱列重複序列的迴歸係數則為0.9975。
除此之外,本研究同時也偵測短縱列重複序列中的點突變,以此方法偵測含有點突變的短縱列重複序列片段和未突變的重複片段比較會具有明顯的差異。
論文英文摘要:Short tandem repeats (STRs) composing one to six nucleotides non-randomly distribute throughout the euchromatic genome. Their polymorphisms have been used as a diagnostic marker for cancer and several hereditary neurodegenerative disorders and analysis development of evolution and pedigrees.
In this study, we used DNA ligation and bioluminescence to determine the copy number of the STR. The primer and the probes were ligated when they are complementary to the proper sites of the template containing short tandem repeats. The copy number of the STR is proportional to the ligase activity. The activity of the NAD+-dependent ligase was measured via detection of the AMP release. The AMP release level can be measured using adenylate kinase and pyruvate kinase convert AMP to ATP, which can be quantified by the luminescence generated by luciferase.
The light intensity is proportional to the AMP concentration in the range of 10 to 140nM and the correlation coefficient of is 0.9998 under tested conditions. Furthermore, the light intensity is proportional to the copy number of TTTTC, the tested motif of STR,in the range of 1 to13 and the correlation coefficient was 0.9975. We also detect the point mutation of STRs using the proposed method. The light intensity is significant difference between the STR with point mutation and the wild type
論文目次:摘 要 i
ABSTRACT ii
誌 謝 iv
目 錄 v
表目錄 viii
圖目錄 ix
第一章 緒論 - 1 -
1.1前言.. - 1 -
1.2研究動機及目的 - 4 -
第二章 研究背景與原理介紹 - 5 -
2.1短縱列重複序列(short tandem repeat) - 5 -
2.1.1短縱列重複序列分類及功能 - 5 -
2.1.2短縱列重複序列的多型性 - 9 -
2.1.3單一核苷酸多型性(single nucleotide polymorphisms) - 13 -
2.1.4 Y-染色體上的STR - 14 -
2.2 偵測STR之方法 - 20 -
2.2.1 偵測STR的發展史 - 20 -
2.2.2 現行STR的檢驗方法 - 22 -
2.2.2.1 毛細管電泳法(capillary electrophoresis) - 22 -
2.2.2.2基質輔助雷射脫附游離飛行時間質譜儀 - 23 -
(Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometer, MALDI-TOF MS) - 23 -
2.2.3 現行SNP的檢驗方法 - 24 -
2.2.3.1 螢光5’端核酸酶反應(TaqMan 5’nuclease assay) - 24 -
2.2.3.2 微序列分析方法Minisequencing(SNaPhotTM Assay) - 25 -
2.3焦磷酸測序(Pyrosequencing) - 27 -
2.3.1原理 - 27 -
2.3.2發展與應用 - 28 -
2.4 DNA連接酶(DNA ligase) - 32 -
第三章 實驗方法與步驟 - 34 -
3.1實驗架構 - 34 -
3.2以連結酵素連接短縱列重複序列 - 38 -
3.2.1膠體製備 - 38 -
3.2.2購買電泳緩衝液 - 38 -
3.2.2.1. TAE buffer - 38 -
3.2.2.2. TBE buffer - 38 -
3.2.3 連結反應 - 38 -
3.2.4膠體電泳 - 39 -
3.3定量AMP - 40 -
3.3.1 CTP標準曲線 - 40 -
3.3.2不同CTP濃度與AMP反應之標準曲線 - 40 -
3.4 定量短縱列重複序列 - 41 -
3.4.1定量待測之DNA分子 - 41 -
3.4.2製備單股DNA分子 - 42 -
3.4.3將PCR產物進行連結反應 - 43 -
3.4.4將釋放的單磷酸腺苷轉換成三磷酸腺苷 - 44 -
  3.5偵測具突變點的短縱列重複序列 - 45 -
3.6定量同濃度範圍的AMP濃度 - 46 -
3.7實驗藥品與設備 - 47 -
3.7.1實驗藥品 - 47 -
3.7.2實驗設備 - 49 -
第四章 結果與討論 - 51 -
4.1使用連結酵素連接短縱列重複序列 - 52 -
4.2定量AMP - 53 -
4.2.1 CTP的標準曲線 - 53 -
4.2.2不同的CTP濃度下AMP標準曲線 - 55 -
4.3單磷酸腺苷及單磷三腺苷之標準曲線 - 57 -
4.4短縱列重複序列之定量標準曲線 - 58 -
4.5具突變點的短縱列重複序列 - 59 -
第五章 結論 - 62 -
參考文獻 - 64 -
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論文全文使用權限:同意授權於2013-08-03起公開