title: A Bioinformatics Approach to Prioritize Single Nucleotide Polymorphisms in TLRs Signaling Pathway Genes.
abstract: It has been suggested that single nucleotide polymorphisms (SNPs) in genes involved in Toll-like receptors (TLRs) pathway may exhibit broad effects on function of this network and might contribute to a range of human diseases. However, the extent to which these variations affect TLR signaling is not well understood. In this study, we adopted a bioinformatics approach to predict the consequences of SNPs in TLRs network. The consequences of non-synonymous coding SNPs (nsSNPs) were predicted by SIFT, PolyPhen, PANTHER, SNPs&GO, I-Mutant, ConSurf and NetSurf tools. Structural visualization of wild type and mutant protein was performed using the project HOPE and Swiss PDB viewer. The influence of 5'-UTR and 3'- UTR SNPs were analyzed by appropriate computational approaches. Nineteen nsSNPs in TLRs pathway genes were found to have deleterious consequences as predicted by the combination of different algorithms. Moreover, our results suggested that SNPs located at UTRs of TLRs pathway genes may potentially influence binding of transcription factors or microRNAs. By applying a pathway-based bioinformatics analysis of genetic variations, we provided a prioritized list of potentially deleterious variants. These findings may facilitate the selection of proper variants for future functional and/or association studies.
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Behnam
authors.initials: B
authors.lastname: Alipoor
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hamid
authors.initials: H
authors.lastname: Ghaedi
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mir Davood
authors.initials: MD
authors.lastname: Omrani
authors.affiliation: Department of Medical Genetics, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
authors.forename: Milad
authors.initials: M
authors.lastname: Bastami
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Reza
authors.initials: R
authors.lastname: Meshkani
authors.affiliation: Department of Biochemistry, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Taghi
authors.initials: T
authors.lastname: Golmohammadi
keywords: Bioinformatics; in-silico analysis; single nucleotide polymorphisms; toll- like receptors