Bioinformatics search for genetic markers of socially significant diseases in promoters of human genes

Abstract

Motivation and Aim:The most important for diagnosing genetic susceptibility to human diseases within predictive-preventive personalized participatory (4P) medicine is a search for their genome-wide markers, among which single nucleotide polymorphisms (SNPs) are of the greatest value. Methods and Algorithms: Using a computer-experimental approach, we created our free available Web service SNP_TATA_Comparator (wwwmgs.bionet.nsc.ru/cgibin/mgs/tatascan/start.pl) [1]. Results: It allows to estimate how SNPs effect on the TATA-binding protein (TBP) binding affinity for the 70 bp proximal promoters in front of transcription start sites (TSS) of the human genes within our three-step model of TBP-promoter interaction [2] taking into account both nucleotide context and conformational together with physicochemical features of the B-helical double-stranded DNA [3]. Due to this we examined 15243 SNPs in question that yielded 3229 candidate SNP-markers aggravating or relieving the development of human diseases such as obesity [4], autoimmune disorders [5], subfertility [6], atherosclerosis [7], rheumatoid arthritis [8], hypertension [9], Alzheimer's disease [10], mental disorders [11] as well as SNP-markers of resistance to anticancer chemotherapy were also identified [12]. Conclusion: An independent selective experimental control verification [13,14] shown a significant linear correlation between the in silico-estimated and in vitro-measured values of the TBP-promoter affinity rates (r = 0.77; p < 0.000001).