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研究生:許欽木
研究生(外文):Chin Mu Hsu
論文名稱:雙核酸重複序列在人類染色體21散佈之研究
論文名稱(外文):Spreading of dinucleotide repeats in Human Chromosome 21
指導教授:陳啟清陳啟清引用關係
指導教授(外文):Chi Chen Chen
學位類別:碩士
校院名稱:國立成功大學
系所名稱:生物學系
學門:生命科學學門
學類:生物學類
論文種類:學術論文
論文出版年:1999
畢業學年度:87
語文別:中文
論文頁數:84
中文關鍵詞:微衛星微衛星不穩定GCG程式套組
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摘要
微衛星DNA又稱為簡單重複序列DNA,為一段由1~10個鹼基組成且多次重複的DNA片段。其具有散佈於整個基因組中,並具高度的變異性的特性。然而到目前為止,微衛星的功能尚未被清楚的瞭解。藉由1989年人類基因組計劃的進行,許多人類的序列片段經定序後上傳到Genbank資料庫供研究者分析使用,而由於染色體第21對為人類23對染色體中最小片段的染色體之一,加上唐氏症的影響,使得21對染色體被當成發展基因組技術的最佳典範。
經由GCG程式套組的協助,我們分析244條位在染色體21上的DNA序列,並探討雙核酸重複序列在21對染色體的情況。並且得知,除了(CG)n外,大部分的雙核酸重複序列與Alu序列的距離約在100~1000個鹼基之間。而比較位於21q22.2的唐氏症與染色體21的其他區域,顯示出位於唐氏症區域的雙核酸重複序列數量比染色體其他地區還多,尤其以(AA)最為明顯。探討對於染色體上不同的雙核酸重複序列的長度及數量,藉由馬可夫鏈模式加以解釋,結果發現隨著長度越長的重複序列,其DNA聚合的滑脫率也越高。
此外,在應用方面,篩選出40組含重複序列的片段當成標記使用,並設計出40對引子以方便定出標記的位置,這些標記能對於基因組圖譜的訂定,致病基因的的搜尋,血緣關係的探討及法律醫學鑑定有所助益。

Abstract
Microsatellites are elements that comprise of multiple copies of repeat unit in the range from one to ten base pairs. They are common and polymorphic in eukaryote genome. Although microsatellites in the genome are abundant and divergent, the functions of microsatellites are not well defined.
After the procession of the Human Genome Project in 1989, many sequences of human chromosomes had been sequenced and updated to Genbank. Chromosome 21 is the smallest one in human chromosomes, and highly related to Down Syndrome, it was thought to be the best model for developing genomic technique.
By using the GCG software, we study the spreading of dinucleotide repeats with repeat numbers four times and more in the 244 DNA sequences of chromosome 21. Most of the distances between dinucleotide repeats and Alu sequences are 100~1000 base pairs, except (GC)n repeats. In comparison of the numbers of dinucleotide repeats between Down Syndrome critical region (DSCR) of 21q22.2 and other region of chromosome 21, the number of (AA) n dinucleotide repeats in DSCR are more obvious. In other respects, the differences in repeat the Markov chain model can explain numbers of dinucleotide repeats in chromosome 21. The slippage rate of DNA polymerase is exponential with the repeat numbers of dinucleotide repeats. Forty markers are identified and may be used for the genomic map, the searching of the genes of genetic disease, the probe for pedigree analysis and ascertainment for medical jurisprudence, etc.

目錄
中文摘要………………………………………………………I
英文摘要…………………………………………………….III
圖目錄……………………………………………………….IV
表目錄………………………………………………………VII
第一章 前言………………………………………………….1
第二章 文獻探討…………………………………………….3
第一節 重複序列的簡介……………………………..….3
第二節 重複序列的不穩定性………………………7
第三節 重複序列不穩定的可能機制………………….10
第四節 重複序列的應用……………………………….12
第五節 生物資訊的結合……………………………….13
第三章 材料與方法………………………………………...15
第一節 材料…………………………………………….15
第二節 方法…………………………………………….18
第四章 結果與討論……………………………………..….21
第一節 Alu序列跟雙核酸重複序列之間距離的
相關性探討……………………………………22
第二節 唐氏症區域(D region)與染色體21其他區域(E region)的雙核酸重複序列比較……………24
第三節 標訂標記………………………………………26
第四節 染色體21雙核酸重複序列的比較………..28
參考文獻……………………………………………………63
附錄…………………………………………………………75

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