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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 蘇怡寧(Yi-Ning Su) | |
| dc.contributor.author | Pei-fen Chen | en |
| dc.contributor.author | 陳佩芬 | zh_TW |
| dc.date.accessioned | 2021-05-20T19:59:29Z | - |
| dc.date.available | 2010-09-09 | |
| dc.date.available | 2021-05-20T19:59:29Z | - |
| dc.date.copyright | 2010-09-09 | |
| dc.date.issued | 2010 | |
| dc.date.submitted | 2010-06-11 | |
| dc.identifier.citation | 1. THOMPSON& THOMPSON GENETICS IN MEDICINE 6th edition
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Kirov, et al Rare chromosomal deletions and duplications increase risk of schizophrenia Nature 455, 237-241 (11 September 2008) 19. S.A McCarroll, Alan Huett , Petric Kuballa, Shannon D Chilewski , et al Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease Nature Genetics 40, 1107 - 1112 (2008) 20. Gonzalez E., Kulkarni H., Bolivar H., Mangano A., Sanchez R., Catano G., Nibbs R.J., Freedman B.J., Quinones M.P., Bamshed M.J., et al. The influence of CCL3L1 gene—containing segmental duplications on HIV-1/AIDS susceptibility. Science 2005:307:1434–1440. 21. Cristen J Willer, Elizabeth K Speliotes, Ruth JF Loos, Shengxu Li, Cecilia M Lindgren. et. al Six new loci associated with body mass index highlight a neuronal influence on body weight regulation Nature Genetics 2009: 41 , 25 - 34 22. Conrad,D.F., Andrews, T.D., Carter, N.P., Hurles, M.E., and Pritchard, J.K. A high- resolution survey of deletion polymorphism in the human genome. 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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/8664 | - |
| dc.description.abstract | 基因組劑量變異(Copy Number Variation)是人類遺傳變異的主要來源，它會造成孟德爾遺傳性狀、散發性性狀，可能與某些複雜性疾病相關，但也代表著個體間良性的多型性變異。然而，亞洲族群基因組劑量變異的訊息仍然有限，我們使用CMDX Bac Array CA2500/ CA3000來鑑別台灣族群1015個個體其CNV的分布，總計發現了438個發生CNV訊號的位置，其中有6個區域其CNV的發生率超過20%，而大多數CNV(92.44%)的變異範圍小於1 Mb，平均每個個體發生CNV的次數為4.36次。發生CNV的區域中，有54.79%和片段性重複序列的位置重疊；64.49%覆蓋基因；92.47%已在相關的文獻報告過，只有7.53%是首次在此篇研究中發現。和先前的文獻相較，Bac Array所偵測的CNVs比高解析度的平台要少的多，但正因為如此，可以降低臨床病理診斷的干擾，因此此篇文獻所使用的Bac Array較適合用於產前、臨床診斷。此篇研究建立屬於台灣族群的CNV圖譜，補足CNV資料庫的族群變異性，可供作臨床遺傳諮詢的參考。 | zh_TW |
| dc.description.abstract | Copy number variation is a source of genetic diversity in humans. CNVs can cause Mendelian or sporadic traits, be associated with complex disease, also represent benign polymorphic variants between individuals. However, CNVs information of Asian populations remains unexplored. We identified CNV distribution of 1015 individuals in Taiwan populations by using CMDX Bac Array CA2500/ CA3000 and find 438 loci with CNV signals. The CNV frequencies of six regions are over 20%. Most CNVs (92.44%) size are shorter than 1 Mb. Average CNV number in each individual is 4.36. Among CNV regions, 54.79% regions overlap with segmental duplication, 64.49% regions cover gene, 92.47% regions are reported in previous study, only 7.53% regions are novel in this study. In contrast to previous studies, CNVs identified are much less than the platform with high resolution. But it lower disturbance in clinical pathologic diagnosis for this reason. So, Bac array used in this study is more appropriate for prenatal, clinical diagnosis. This study establish CNV map of Taiwan populations for further reference of genetic consulting. | en |
| dc.description.provenance | Made available in DSpace on 2021-05-20T19:59:29Z (GMT). No. of bitstreams: 1 ntu-99-P97448004-1.pdf: 1489729 bytes, checksum: b392ac6d982b70dc58a13a58c332d136 (MD5) Previous issue date: 2010 | en |
| dc.description.tableofcontents | 口試委員會審定書…………………………………………………… I
誌謝…………………………………………………………………… II 中文摘要……………………………………………………………… III 英文摘要……………………………………………………………… IV 內文目錄……………………………………………………………… V 圖目錄………………………………………………………………… VII 表目錄………………………………………………………………… IX 第一章 研究背景與動機…………………………………………… 1 第一節 顯微鏡下的結構變異……………………………………… 1 第二節 次顯微結構變異…………………………………………… 3 第三節 結構變異的類型…………………………………………… 4 第四節 基因組劑量變異(CNV)形成的機制………………………… 9 第五節 基因組劑量變異(CNV)如何影響表型變化……………… 10 第六節 基因組劑量變異(CNV)對個體表型及疾病易感性的影響…12 第七節 基因組劑量變異(CNV)的臨床意義與重要性………………13 第八節 偵測基因組劑量變異(CNV)的方法…………………………15 第九節 近期文獻對基因組劑量變異(CNV)的研究…………………20 第十節 研究目的與動機…………………………………………….24 第二章 研究方法………………………………………………………26 第一節 研究樣本來源……………………………………………… 26 第二節 以CMDX Bac Array CGH分析基因組中的劑量變異……… 26 第三節 以Competitive Multi-Plex PCR 驗証CMDX Bac Array的基因組劑量變異訊號…………………………………… 30 第四節 與現有基因組變異資料庫進行比對……………………… 32 第三章 結果………………………………………………………… 34 第四章 討論………………………………………………………… 43 第五章 結論………………………………………………………… 50 參考文獻……………………………………………………………… 51 附錄：台灣族群CNV發生位置與頻率一覽表………………………… 56 圖 目 錄 圖一：CGH與aCGH的操作原理………………………………………… 18 圖二：Bac Array CGH的操作流程…………………………………… 29 圖三：人類基因組變異資料庫http://projects.tcag.ca/variation搜尋介面…………………………………………………………………32 圖四：Bac Clone: CTD-2041D13 (Chr5:69364823-69448911)於資料庫的搜尋結果……………………………………………………………33 圖五：樣本509的全基因組基因組劑量變異掃描結果圖…………… 34 圖六：樣本313-2在Chr 6的aCGH結果Deletion表現…………………35 圖七：參考檢體在6p25.3/ DUSP22 gene的劑量…………………… 35 圖八：樣本313-2第一次Multi-Plex PCR結果……………………… 35 圖九：樣本313-2第二次Multi-Plex PCR結果……………………… 35 圖十：樣本H268在Chr 6的aCGH結果eletion表現………………… 36 圖十一：參考檢體在6p25.3/ DUSP22 gene的劑量………………….36 圖十二：樣本H268在6p25.3/ DUSP22 gene的Deletion表現……… 36 圖十三：樣本H490在的Chr 4的aCGH結果Duplication表現……… 36 圖十四：參考檢體在4p16.1/ CPZ gene的劑量表現…………………36 圖十五：樣本H490在4p16.1/ CPZ gene的Duplication表現……… 36 圖十六：樣本321在的Chr 12的aCGH結果Duplication表現……… 37 圖十七：參考檢體在12p12.3/ RERG gene的劑量表現…………… 37 圖十八：樣本321在12p12.3/ RERG gene的Duplication表現…… 37 圖十九：參考檢體在12p12.3/ PIK3C2G gene的劑量表現………… 37 圖二十：樣本321在12p12.3/ PIK3C2G gene的Duplication表現… 37 圖二十一：台灣族群基因組基因組劑量變異分佈……………….… 38 圖二十二：台灣族群常見發生基因組劑量變異的位置Incidence>1%） ………39 圖二十三：台灣族群全基因組劑量變異形式分析………………… 40 圖二十四：台灣族群基因組劑量變異的基因覆蓋率……………… 41 圖二十五：台灣族群基因組劑量變異與Segmental Duplication的重疊率…………………………………………………… 41 圖二十六：台灣族群已知CNV與新發現的CNV比例………………… 41 圖二十七：台灣族群基因組劑量變異的大小變化與分佈………… 42 圖二十八：在染色體9、15、16所觀察到的Heteromhorphism…… 45 圖二十九：多型性CNV的鑑別流程…………………………………… 47 表 目 錄 表一：分析檢體來源一覽表………………………………………… 34 表二：個體的平均基因組劑量變異………………………………… 34 表三：在健康個體所看到的CNV，部分座於相關遺傳疾病的致病位置…………………………………………………………… 44 表四：研究結果與相關文獻的比較 (C表示中國人；J表示日本人；K表示韓國人)……………………………………………… 49 | |
| dc.language.iso | zh-TW | |
| dc.title | 台灣族群全基因組劑量變異分析：建立供作臨床與研究應用的數據資料 | zh_TW |
| dc.title | Whole Genome Analysis of Copy Number Variations in Taiwan Populations: A Data Resource for Clinical and Research Applications | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 98-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 楊偉勛(Wei-Shin Young),林炫沛 | |
| dc.subject.keyword | 基因組劑量變異,良性變異,非等位同源重組,非同源末端連結,比較式基因組雜交技術, | zh_TW |
| dc.subject.keyword | Copy Number Variation,Heteromorphism,Non-Allelic Homomlogous Recombination,Non Homologous End Junction,Comparative Genomic Hybridization, | en |
| dc.relation.page | 75 | |
| dc.rights.note | 同意授權(全球公開) | |
| dc.date.accepted | 2010-06-11 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| 顯示於系所單位： | 分子醫學研究所 | |
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