生物資源暨農學院: 生物產業機電工程學研究所指導教授: 陳倩瑜黃哲栩Hwang, Je-ShiuJe-ShiuHwang2017-03-022018-07-102017-03-022018-07-102016http://ntur.lib.ntu.edu.tw//handle/246246/272499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。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.1155883 bytesapplication/pdf論文公開時間: 2021/8/25論文使用權限: 同意有償授權(權利金給回饋本人)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-synonymousTranscription factor binding sites1000 genome projectTaiwan genomesinformation contentconsensus pattern[SDGs]SDG3thesis10.6342/NTU201603119http://ntur.lib.ntu.edu.tw/bitstream/246246/272499/1/ntu-105-R03631004-1.pdf