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The TNF-α gene mutations are seen in many diseases especially inflammatory diseases. Hence, before planning a larger population study, it is advisable to sort out the possible functional SNPs. To accomplish this goal, data available in the dbSNP database and different computer programs can be used. Therefore, this study was undertaken to find the functional nsSNPs (non-synonymous single nucleotide polymorphisms) in TNF-α. Out of the total 169 SNPs, 48 were nsSNPs (non-synonymous single nucleotide polymorphisms), 23 occurred in the mRNA 3' UTR, 10 occurred in 5' UTR region, 41 occurred in intronic regions and the rest were other types of SNPs. SIFT and PolyPhen predicted 2 out of 48 nsSNPs as damaging. Among the predicted nsSNPs, rs4645843 and rs1800620 were identified as deleterious and damaging by the SIFT (Sorting Intolerant from Tolerant) and PolyPhen programs. Additionally, I-Mutant and nsSNPAnalyzer showed a decrease in stability for these nsSNPs upon mutation. Protein structural analysis with these amino acid variants was performed by using I-Mutant, Swiss PDB viewer, ANOLEA (Atomic Non-Local Environment Assessment), MUSTER (MUlti-Sources ThreadER) and NOMAD-Ref servers to check their molecular dynamics and energy minimization calculations. This study suggested that P84L and A94T variants of TNF-α could directly or indirectly destabilize the amino acid interactions and hydrogen bond networks thus explaining the functional deviations of protein to some extent.
Pubmed ID: 25606441
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Database as central repository for both single base nucleotide substitutions and short deletion and insertion polymorphisms. Distinguishes report of how to assay SNP from use of that SNP with individuals and populations. This separation simplifies some issues of data representation. However, these initial reports describing how to assay SNP will often be accompanied by SNP experiments measuring allele occurrence in individuals and populations. Community can contribute to this resource.
View all literature mentionsPortal which provides access to scientific databases and software tools (i.e., resources) in different areas of life sciences including proteomics, genomics, phylogeny, systems biology, population genetics, transcriptomics etc. It contains resources from many different SIB groups as well as external institutions.
View all literature mentionsSoftware tool which predicts possible impact of amino acid substitution on structure and function of human protein using straightforward physical and comparative considerations. PolyPhen-2 is new development of PolyPhen tool for annotating coding nonsynonymous SNPs.
View all literature mentionsCollection of structural data of biological macromolecules. Database of information about 3D structures of large biological molecules, including proteins and nucleic acids. Users can perform queries on data and analyze and visualize results.
View all literature mentionsData analysis service to predict whether an amino acid substitution affects protein function based on sequence homology and the physical properties of amino acids. SIFT can be applied to naturally occurring nonsynonymous polymorphisms and laboratory-induced missense mutations. (entry from Genetic Analysis Software) Web service is also available.
View all literature mentionsSoftware tool as Program for Comparative Protein Structure Modelling by Satisfaction of Spatial Restraints. Used for homology or comparative modeling of protein three dimensional structures. User provides alignment of sequence to be modeled with known related structures and MODELLER automatically calculates model containing all non hydrogen atoms.
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