Software pipeline for the analysis of the functional role of nucleotide substitutions in regulatory regions of genes and its testing on polymorphisms associated with obesity

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Ekaterina Alekseevna Matrosova¹, Vadim Mikhailovich Efimov², Elena Vasilevna Ignatieva^3
1Novosibirsk State University, MatrosovaEA@bionet.nsc.ru
²ICG SB RAS, efimov@bionet.nsc.ru
³ICG SB RAS, eignat@bionet.nsc.ru

Genome-wide association studies have shown that approximately 90% of the nucleotide substitutions associated with diseases are located outside the coding regions of the genes, with about 40% occurring in regulatory regions. However, the molecular mechanisms by which such SNPs influence incidence of diseases are still poorly understood. In this work, we have developed a software pipeline that allows us to predict the potential effects of nucleotide substitutions on potential transcription factor binding sites (TFBSs). This pipeline integrates and analyzes information obtained from the UCSC Variant Annotation Integrator and PERFECTOS-APE programs, and the dbSNP, Ensembl and HOCOMOCO databases. The operation of the pipeline was tested on two sets of SNPs. All of them were located in the BDNF gene regulatory regions in the vicinity of the SNP rs11030104 associated with elevated body weight. SNPs from the first set were in linkage disequilibrium with rs11030104 and the second set contained random SNPs. We found some differences in the functional characteristics of TFBSs and corresponding transcription factors identified on the basis of the analysis of these two sets of SNPs.