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DC 欄位 | 值 | 語言 |
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dc.contributor.advisor | 陳倩瑜 | |
dc.contributor.author | Je-Shiu Hwang | en |
dc.contributor.author | 黃哲栩 | zh_TW |
dc.date.accessioned | 2021-06-15T11:12:52Z | - |
dc.date.available | 2021-08-25 | |
dc.date.copyright | 2016-08-25 | |
dc.date.issued | 2016 | |
dc.date.submitted | 2016-08-21 | |
dc.identifier.citation | 1. N. Siva. 2008. 1000 Genomes project. Nature biotechnology. 26(3): 256-256.
2. E. Wingender, et al. 2000. TRANSFAC: an integrated system for gene expression regulation. Nucleic acids research. 28(1): 316-319. 3. F.H. Crick, J.S. Griffith, and L.E. Orgel. 1957. Codes without commas. Proceedings of the National Academy of Sciences of the United States of America. 43(5): 416. 4. F. Crick. 1970. Central dogma of molecular biology. Nature. 227(5258): 561-563. 5. G.D. Winter. 2011. Three Waves Of Innovation In Vertebrate Evolution. Available at: http://www.science20.com/curious_cub/three_waves_innovation_vertebrate_evolution-81858. Accessed 20 August 2011. 6. G.D. Stormo, et al. 1982. Use of the ‘Perceptron’algorithm to distinguish translational initiation sites in E. coli. Nucleic Acids Research. 10(9): 2997-3011. 7. P.J. Farnham. 2009. Insights from genomic profiling of transcription factors. Nature Reviews Genetics. 10(9): 605-616. 8. A. McKenna, et al. 2010. The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data. Genome research. 20(9): 1297-1303. 9. G.P. Consortium. 2012. An integrated map of genetic variation from 1,092 human genomes. Nature. 491(7422): 56-65. 10. C.-T. Fan, J.-C. Lin, and C.-H. Lee. 2008. Taiwan Biobank: a project aiming to aid Taiwan’s transition into a biomedical island. Pharmacogenomics. 9(2): 235-246. 11. M. Bamshad, et al. 2004. Deconstructing the relationship between genetics and race. Nature Reviews Genetics. 5(8): 598-609. 12. E.G. Burchard, et al. 2003. The importance of race and ethnic background in biomedical research and clinical practice. New England Journal of Medicine. 348(12): 1170-1175. 13. R.S. Cooper, J.S. Kaufman, and R. Ward. 2003. Race and genomics. New England Journal of Medicine. 348(12): 1166-1169. 14. M.W. Foster and R.R. Sharp. 2002. Race, ethnicity, and genomics: social classifications as proxies of biological heterogeneity. Genome Research. 12(6): 844-850. 15. A.H. Goodman. 2000. Why genes don't count (for racial differences in health). American Journal of Public Health. 90(11): 1699. 16. N.A. Rosenberg, et al. 2002. Genetic structure of human populations. science. 298(5602): 2381-2385. 17. L.B. Jorde and S.P. Wooding. 2004. Genetic variation, classification and'race'. Nature genetics. 36: S28-S33. 18. J.L. Mountain and N. Risch. 2004. Assessing genetic contributions to phenotypic differences among'racial'and'ethnic'groups. Nature genetics. 36: S48-S53. 19. R.A. Gibbs, et al. 2003. The international HapMap project. Nature. 426(6968): 789-796. 20. ISGR. 2008. The International Genome Sample Resource. Available at: http://www.1000genomes.org/about. Accessed 12 October 2015. 21. T. Biobank. 2012. Taiwan Biobank. Available at: http://www.twbiobank.org.tw/new_web/about.php. Accessed 1 May 2016. 22. S.C. Kent WJ, Furey TS, Roskin KM, Pringle TH, Zahler AM, Haussler D. 2002. The human genome browser at UCSC. Available at: https://genome.ucsc.edu/. Accessed 12 October 2015. 23. R. Ihaka and R. Gentleman. 1996. R: a language for data analysis and graphics. Journal of computational and graphical statistics. 5(3): 299-314. 24. G.E. Crooks, et al. 2004. WebLogo: a sequence logo generator. Genome research. 14(6): 1188-1190. 25. W. McLaren, et al. 2016. The Ensembl Variant Effect Predictor. Genome Biology. 17(1): 1-14. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/48979 | - |
dc.description.abstract | 基因調控在生物體當中是非常重要的機制。基因調控可分為很多部分,其中以轉錄因子與轉錄因子結合位的相互作用下,使得其後方的基因表現被活化或抑制之議題最為關鍵。透過探討轉錄因子本身與其結合位的差異,對於找出影響基因表現的原因更加有幫助。於2008年,千人基因組計畫的誕生,透過蒐集全世界超過1000人的基因序列,建立大型的人類基因資料庫。隨著生物資料庫的建立,各國家也開始建立自己國家人種的生物資料庫;台灣在2005年也展開了生物資料庫的進行,迄今總共收錄了67692的案件,並追蹤4350人的健康資訊,而這些數字仍持續上升當中。本論文使用千人基因組與台灣個人基因體的資料,並搭配TRANSFAC資料庫提供的轉錄因子結合為資訊,探討落在轉錄因子結合位的變異位點在不同人種有何差異。結果顯示東亞族群與台灣人種的變異位點相似度甚高,另外也鑑定出部分的台灣人種特有變異會發生在轉錄因子結合位中的高鹼基保留性位置,顯示這些位置的鹼基被替換後有可能會對所在的轉錄因子結合位造成影響。另外,本論文亦透過檢視落在基因編碼區且屬於台灣人種特有的變異位點,整理與條列出於這些變異位點中屬於non-synonymous mutation,而造成轉譯出的轉錄因子蛋白質序列變異而功能損壞的變異。本論文積累之對於轉錄因子與其結合位的變異位點觀察結果可作為台灣未來發展個人化醫療的重要基礎。 | zh_TW |
dc.description.abstract | Gene regulation plays an important role in biological processes, and involves several regulatory steps. One of the key steps is the event that transcriptions factor binding sites (TFBS) bound by transcription factors (TF), and thus activate or inactivate the target gene expression. To understand TF-related gene regulation, it is essential to investigate genomic variants located within TFBSs or genomic regions that encode transcription factors. This thesis integrates the data from 1000 Genome project, Taiwan biobank, and the TRANSFAC database to discover the genomic variants within TFBSs by comparing the genomic variant information of the different races. The result shows that the variants observed in Eastern Asian are similar to that in Taiwanese. In addition, some variants observed only in Taiwanese are particularly found at the high conserved positions of TFBSs. This reveals that these specific variants may seriously affect TF binding by destroying the original sequence pattern of the TFBSs. Moreover, the Taiwanese-specific variants located in the coding regions of TFs are also investigated by using coding sequences collected from GENCODE. These variants resulting in non-synonymous mutation that may affect the TF functions are listed for future biological validations. In conclusion, this thesis identified Taiwanese-specific variants within TFBSs or genomic regions that encode TFs, which can serves as an important resource for developing personalized medicine in Taiwan. | en |
dc.description.provenance | Made available in DSpace on 2021-06-15T11:12:52Z (GMT). No. of bitstreams: 1 ntu-105-R03631004-1.pdf: 1155883 bytes, checksum: 800966b6a00e5f6cc1d514cef5115240 (MD5) Previous issue date: 2016 | en |
dc.description.tableofcontents | 目錄
論文口試委員審定書 i 誌謝 ii 摘要 iv Abstract v 目錄 vi 圖目錄 viii 表目錄 ix 第一章 研究目的 1 第二章 文獻探討 2 2.1 分子生物學中心法則 2 2.2 轉錄因子(transcription factor) 3 2.2.1 轉錄因子結合位(transcription factor binding site) 3 2.2.2 位置頻率矩陣(position frequency matrix, PFM) 4 2.2.3 TRANSFAC資料庫 5 2.2.4 啟動子(promoter) 6 2.3 基因編碼序列(Coding Sequence) 8 2.3.1 Synonymous與Non-synonymous 8 2.4 次世代定序(Next Generation Sequencing) 10 2.4.1 染色質共免疫沉澱定序(ChIP-Seq) 10 2.5 變異識別(variant calling) 12 2.6 千人基因體計畫(1000 genome project) 13 2.7 台灣個人基因體資料 14 2.8 人種基因差異探討 15 第三章 研究方法 17 3.1 資料庫 17 3.1.1 千人基因組資料 17 3.1.2 台灣個人基因體資料 20 3.1.3 TRANAFAC資料庫 20 3.1.4 參考基因組 22 3.2 實驗流程 22 3.2.1 變異位點資訊比對及分群 23 3.2.2 計算Allele Frequency及統計檢定 25 3.2.3 台灣族群探討 27 3.2.4 資訊含量(Information Content) 28 第四章 結果與討論 29 4.1 基本資料統計 29 4.1.1 千人基因組與台灣個人基因體資料統計 29 4.1.2 TRANSFAC資料庫提供的轉錄因子結合位資料 31 4.1.3 落於轉錄因子結合位之變異位點資訊統計 34 4.2 人種相似度探討 34 4.3 台灣族群分析結果探討 37 4.4 轉錄因子結合位發生台灣特有變異位點之探討 39 4.5 台灣特有之變異位點對於蛋白質轉譯影響之探討 42 第五章 結論 44 參考文獻 45 圖目錄 圖2-1 分子生物學中心法則示意圖,摘自文獻[4] 2 圖2-2 轉錄因子與其結合位之示意圖,摘自文獻[5] 4 圖3-1 TRANSFAC資料庫提供之轉錄因子結合位資訊 (向下箭頭表示換行) 21 圖3-2 TRANSFAC資料庫提供之轉錄因子結合位之矩陣資訊(向下箭頭表示換行) 21 圖3-3 實驗流程圖 23 圖3-4 VCF檔案格式 25 圖3-5 變異位點於不同人種之Allele Frequency 26 圖4-1 千人基因組與台灣個人基因體人數量表 31 圖4-2 TRANSFAC 轉錄因子結合位長度分布圖 33 圖4-3 各人種對整體之Allele Frequency於染色體13之差異性比較熱圖(heatmap) 36 圖4-4 各人種對整體之Allele Frequency於染色體14之差異性比較熱圖(heatmap) 36 圖4-5 台灣特有、特多、特少Allele Frequency之boxplot 38 圖4-6 台灣特多p-value與Allele Frequency分布圖 38 圖4-7 台灣特有資訊含量之長條圖 40 圖4-8 台灣特有之Allele Frequency長條圖 40 圖4-9 台灣特有之資訊含量與Allele Frequency分布圖 41 圖4-10 台灣特有變異位點可能影響蛋白質變異之Allele Frequency長條圖 43 表目錄 表3-1 千人基因組計畫地區統計人數表 18 表4-1 不同人種於各染色體內之位點變異數量表 30 表4-2 TRANSFAC提供之轉錄因子結合位(TFBS)資訊 32 表4-3 TRANSFAC提供之轉錄因子結合位長度數量分布表 33 表4-4 千人基因組與台灣個人基因體變異位點落於轉錄因子結合位之統計 35 表4-5 台灣特多、特少、特有之變異位點統計表 37 表4-6 台灣特有變異位點中資訊含量高及Allele Frequency高之位點詳細資訊 41 表4-7 VEP預測數量表 42 表4-8 台灣特有Allele Frequency高之變異位點及其蛋白質詳細資訊 43 | |
dc.language.iso | zh-TW | |
dc.title | 使用千人基因體與台灣個人基因體資料探討不同人種之轉錄因子結合位差異 | zh_TW |
dc.title | Investigating Variations of Transcription Factor Binding Sites in Human Races Using 1000 Genomes and Taiwan Genomes Data | en |
dc.type | Thesis | |
dc.date.schoolyear | 104-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳沛隆,蘇中才,吳君泰 | |
dc.subject.keyword | 轉錄因子結合位,千人基因組,台灣個人基因體,TRANSFAC,資訊含量,共識特徵,non-synonymous, | zh_TW |
dc.subject.keyword | Transcription factor binding sites,1000 genome project,Taiwan genomes,TRANSFAC,information content,consensus pattern,non-synonymous, | en |
dc.relation.page | 46 | |
dc.identifier.doi | 10.6342/NTU201603119 | |
dc.rights.note | 有償授權 | |
dc.date.accepted | 2016-08-22 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 生物產業機電工程學研究所 | zh_TW |
顯示於系所單位: | 生物機電工程學系 |
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