臺灣博碩士論文加值系統

　　三核甘酸重複序列 (trinucleotide repeats; TNRs) 為重複單元由三個鹼基所形成之縱列式重複序列 (tandemly repeated sequence) 。近年來，有愈來愈多的證據顯示三核甘酸重複序列的不穩定擴張現象會引起許多人類遺傳疾病。因此對於其在基因組中定位及相關分佈特性的研究就顯得刻不容緩。本研究主要藉由GCG伺服器與自行開發之搜尋軟體，針對人類第22條染色體中20種三核甘酸重複序列進行分析，目的在於建立其高解析度分佈圖譜，並探討與第21條染色體之相關分佈特性之差異。
　　結果顯示CAC/GTG/CTC/GAG為出現頻率與覆蓋率最高的重複序列種類，至於相對距離則與出現頻率呈現高度反相關性，多半集中於5~50kb以內，顯示其廣泛分佈的特性，且有24.18%的三核甘酸重複序列位於基因區內。透過馬可夫連鎖模式 (Markov chain model) 的應用，三核甘酸重複序列之最佳分佈模式自重複4次起，皆吻合期望值的分佈，且出現較高之最大長度的重複種類，通常也伴隨較高的DNA聚合酶滑脫率，這顯示DNA聚合酶滑脫效應的確參與三核甘酸重複序列擴張的過程。最後在與第21條染色體之比較中，由於兩條染色體之G+C content差異頗大，進而造成相異之三核甘酸重複序列的分佈特性。盼望藉由此研究能更深入瞭解微衛星DNA在人類基因組中所可能扮演的角色，並對於相關的研究能有所助益。

　　Trinucleotide repeats (TNRs) , which repeat unit consists of three nucleotide base-pair, are one member of tandemly repeated sequences. In the past few years, more and more evidences had been approved that instable expansion of certain TNRs may be the cause of many human inheritable diseases. Therefore, it is of great urgency to investigate the location and distribution properties of TNRs within the whole human genome. In this thesis, I construct the chromosome positioning system of all twenty kinds of TNRs in human chromosome 22 q-arm by both GCG server and search software developed by ourselves. The goals of this research are not only to build high resolution map of TNRs in human chromosome 22, but to proceed profile comparison with chromosome 21.
　　The results indicate the CAC/GTG/CTC/GAG repeat patterns own the highest frequency and coverage of TNRs. Further, the adjacent distance and appearance present high inverse proportion. The relationship confirms the widespread property of TNRs, which distribute mostly within 5 to 50 kb. Besides, 24.18 percent of TNRs locate in gene regions of human chromosome 22. By Markov chain model, since repeat number (n) ≧ 4, the best-fit models deduced from observed values match expected values almost. Moreover, by longer repeat length patterns usually accompanying higher DNA polymerase slippage rate, I conclude the DNA polymerase slippage event would actually involve in expansion process of TNRs. Finally, in the profile comparison aspect, the different completely distribution properties of TNRs between human chromosome 21 & 22 is not beyond my expectations because of the dissimilar G+C content. Hope this thesis be helpful and useful to related research field for elucidating more deeply the important roles of microsatellite DNA in human genome.

目錄
中文摘要
英文摘要
誌謝
表目錄....................................................................................I
圖目錄................................................................................III
第一章 文獻回顧.................................................................1
第一節 縱列式重複序列之種類...............................................1
第二節 微衛星DNA之簡介.....................................................3
第三節 微衛星DNA扮演之生物功能與應用.........................4
第四節 微衛星DNA之不穩定性與人類疾病的關係.............8
第五節 人類基因體計劃.........................................................13
第六節 後基因組學時代與生物資訊學.................................16
第二章 研究動機與目的...................................................18
第三章 材料與方法...........................................................19
第一節 研究材料.....................................................................19
第二節 研究方法之邏輯架構.................................................21
第四章 結果.......................................................................25
第一節 三核甘酸重複序列高解析分佈圖譜之建立.............25
第二節 三核甘酸重複序列之出現頻率與最大長度.............27
第三節 三核甘酸重複序列之覆蓋率.....................................29
第四節 三核甘酸重複序列位於基因區與非基因區之差異.31
第五節 三核甘酸重複序列片段相對距離之分佈.................32
第六節 三核甘酸重複序列最佳分佈模式之建立與DNA聚合酶滑脫率之計算....................................................34
第五章 三核甘酸重複序列於人類第21與22條染色體之分析結果比較.......................................................37
第一節 三核甘酸重複序列出現頻率與最大長度之比較.....37
第二節 三核甘酸重複序列覆蓋率之比較.............................38
第三節 三核甘酸重複序列基因區分佈比例之比較.............38
第四節 三核甘酸重複序列DNA聚合酶滑脫率之比較.......39
第六章 討論.......................................................................40
參考文獻...........................................................................108
附錄
自述

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