Polymorphisms in the transcription factor binding sites of host genes influences evolutionary susceptibility to falciparum malaria

摘要

Gene expression at the level of transcription is regulated by a set of transcription factors (TFs) that recognizes?cis?elements. We accessed the human promoters from eukaryotic promoter database. These sequences have been run in P-match tool. MEME software has been used for detection of conserved sequences in the promoter region. All the predicted known TFs and their binding sites along with weight matrices were collected from TRANSFAC database under vertebrate TFs category. P-match tool combines pattern matching and weight matrix approaches thus providing higher accuracy of recognition than each of the methods alone. P-Match is closely interconnected with the TRANSFAC? database. Using results of extensive tests of recognition accuracy, we selected three sets of optimized cut-off values that minimize either false negatives or false positives, or the sum of both errors. ?In this report, we focus on those polymorphisms of transcription factor binding sites (TFBS) in the regulatory region of host genes and hypothesize that these variation increases the susceptibility/resistance to a particular disease by alteration of gene product in the cell. Therefore, we have concluded that 124 promoter polymorphisms in the 9 genes involved in malaria pathogenesis play important role in susceptibility to falciparum malaria.