博碩士論文 952211014 詳細資訊




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姓名 張凱廸(Kai-Di Jhang)  查詢紙本館藏   畢業系所 系統生物與生物資訊研究所
論文名稱 躁鬱症病患的精子之DNA 甲基化的網路分析
(DNA methylation Network analysis on bipolar disorder sperm)
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摘要(中) 躁鬱症是常見的一種複雜型精神疾病。它透過體染色體及X染色體在家族的個體中遺傳,除此之外它也受到環境因素影響,如化學要素或情緒壓力等。DNA甲基化在表觀遺傳學中佔重要角色,它在DNA遺傳序列以外建立改變生物性狀並且可以遺傳的機制。於是我們以偵測DNA甲基化的CpG 小島微陣列晶片(包含13056個探針) 來分析躁鬱症病患與正常人精子裡DNA甲基團的分佈,並藉由統計學裡的淨相關來計算微陣列數據中探針間的相關性。無論是質譜儀、基因體染色質免疫沉澱或是其他高通量實驗數據,圖型模型是一個適合資料探勘與整合的分析方式。我們以圖型化高斯模型來表示這些CpG小島中甲基團密度變化量的相依性,並且探討圖型結構中的特性 ─ 模數、度協調、叢集係數等─及註解其生物意義。
摘要(英) Manic depression disorder is a complex heritable disease in that its heredity comes from genetic abnormalities in somatic and X chromosomes. Beside genetic factor, environment factors also affect the disease’’s susceptibility. DNA methylation plays a role in epigenetics and is considered to serve as a bridge between genetic and environmental factors. In this thesis, we describe a genome-wide DNA methylation dataset of 19 bipolar disorder (manic depression) and 18 normal individuals using human CpG island microarrays (containing 13056 probes). Then we analyze the methylation relations among the measuring probes using Graphical Gaussian models for each phenotypic group, obtaining networks of co-methylation. Modularity, assortativity and clustering coefficient properties of the networks are calculated. Genes involved in co-methylation are grouped and annotated by Gene Ontology terms. Candidate genes have some implications to the disorder.
關鍵字(中) ★ DNA甲基化
★ CpG小島
★ 網路分析
★ 躁鬱症
★ 表觀遺傳學
★ 淨相關
★ 微陣列
★ 圖形化高斯模型
關鍵字(英) ★ DNA microarray
★ partial correlation
★ cpg island
★ DNA methylation
★ epigenetic
★ bipolaar disorder
★ Manic depression
★ graphical gaussian model
★ network
論文目次 中文摘要 ............................I
英文摘要 ............................II
誌謝詞 ............................III
目錄 ............................IV
圖目錄 ............................V
表目錄 ............................VI
壹、研究背景介紹............................1
1-1 表觀遺傳學 (epigenetics) ............................1
1-1-1 遺傳性質 ............................3
1-2 DNA甲基化與DNA甲基轉移酶 ............................5
1-3 印記作用 (imprinting)與X染色體失活 (X-inactivation) ............................10
1-3-1 印記作用 (imprinting) ............................10
1-3-2 X染色體失活 (X chromosome inactivation) ............................13
1-4 表觀遺傳學與精神疾病 ............................15
貳、研究方法與材料............................18
2-1 CpG 微陣列實驗 (CpG microarray experiment) ............................18
2-2 圖形式高斯模型 (Graphical Gaussian models) ............................20
2-3模數 (modularity)、度協調 (assortativity)、叢集係數(clustering coefficient) ............................23
2-4 GO term overrepresentation ............................26
參、結果 ............................29
肆、結論 ............................39
伍、參考文獻 ............................41
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指導教授 王孫崇(Sun-chong Wan) 審核日期 2008-7-18
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