In silico discrimination of nsSNPs in hTERT gene by means of local DNA sequence context and regularity
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Understanding and predicting the significance of novel genetic variants revealed by DNA sequencing is a major challenge to integrate and interpret in medical genetics with medical practice. Recent studies have afforded significant advances in characterization and predicting the association of single nucleotide polymorphisms in human TERT with various disorders, but the results remain inconclusive. In this context, a comparative study between disease causing and novel mutations in hTERT gene was performed computationally. Out of 59 missense mutations, five variants were predicted to be less stable with the most deleterious effect on hTERT gene by in silico tools, in which two mutations (L584W and M970T) were not previously reported to be involved in any of the human disorders. To get insight into the structural and functional impact due to the mutation, docking study and interaction analysis was performed followed by 6 ns molecular dynamics simulation. These results may provide new perspectives for the targeted drug discovery in the coming future.
KeywordsDocking hTERT Molecular dynamics simulation SNPs
The authors take this opportunity to thank the management of Vellore Institute of Technology University for providing the facilities and encouragement to carry out this work.
Conflict of interest
- 2.Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature. 447:661–78Google Scholar
- 3.Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES (1999) Characterization of single-nucleotide polymorphisms in coding regions of human genes. Nat Genet 22:231–238CrossRefGoogle Scholar
- 11.Ly H (2009) Genetic and environmental factors influencing human diseases with telomere dysfunction. Int J Clin Exp Med 2:114–130Google Scholar
- 26.Sherry ST, Ward M, Sirotkin K (1999) dbSNP-Database for Single Nucleotide Polymorphisms and other classes of minor genetic variation. Genome Res 9:677–679Google Scholar
- 42.Flanagan SE, Patch AM, Ellard S (2010) Using SIFT and PolyPhen to predict loss-of-function and gain-of-function mutations. Genet Test Mol Biomarkers 14:533–7Google Scholar