Genome-wide Analysis Of Transcription Factor Binding Sites And Gene Mutation Of Genetic Disease

With the completion of the Human Genome Project, the focus of study shiftsfrom structural genomics to functional genomics. That is to say, in human genomestudy, all the DNA sequences have to be obtained. More importantly, the function ofeach gene should be understood and the relationship between each gene and a certaindisease has to be found. Therefore, how to analysis the vast amounts of genomic datais very important in terms of deciphering gene functions. In this thesis, we mainlyanalyze the transcription factor binding sites and gene mutations of genetic disease ongenome-wide.With the rapid development of bioinformatics, the study on transcription factorbinding sites becomes a hot topic. Transcription factors can control gene transcription,and identification of transcription factor binding sites(TFBS) can help us tounderstand the mechanism of transcription regulation. In this thesis, based on thecompletion of TWIST Chromatin Immunoprecipitation sequencing(ChIP-seq), wepreferred BSMM process, and complete the analysis of TWIST binding sites andE-box on genome-wide. We got26229TWIST binding sites and90659E-boxes.Moreover, through further analysis of chromosome6, we got1936binding sites and6437E-boxes, and genes have been annotated and predicted the binding sites whichdistribute in the promoter region on chromosome6.The Retinitis Pigmentosa is a common Mendelian genetic diseases caused by asingle gene mutation. The incidence of this disease is about1/3500in human.Currently,52genes causing the disease have been found. Based on the completion ofWhole Exon Sequencing(WES), we preferred BSGA process, and complete theanalysis of106RP samples data on genome-wide. We got a total of297577mutations,and2807mutations per sample have been found. Through existing gene databases andliterature, we filter the mutation that we get, and find all possible disease-causingmutations. Finally, we found4new gene mutation candidates.This study is base on Retina Research Foundation in Rui Chen lab, BaylorCollege of Medicine, USA. The sequencing is performed on the platform of Illumina,and data analysis is performed on the Linux platform. Analytical results show that theTWIST ChIP-seq data analysis results of BSMM process provides a scientific basisfor further functional experiments. And the WES data analysis results of BSGAprovides a efficient analysis method for screening rare genetic disease which isdifficult to find the causative gene mutations by regular method; and provide a candidate disease gene for further clinical diagnosis of the disease and gene therapyapplications.