Investigating Variations of Transcription Factor Binding Sites in Human Races Using 1000 Genomes and Taiwan Genomes Data

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.