Abstract
The aim of our study is to identify probable deleterious genetic variations that can alter the expression and the function of the CHRNA3 gene using in silico methods. Of the 2305 SNPs identified in the CHRNA3 gene, 115 were found to be non-synonymous and 12 and 15 nsSNPs were found to be in the 5′ and 3′ UTRs, respectively. Further, out of the 115 nsSNPs investigated, eight were predicted to be deleterious by both SIFT and PredictSNP servers. The major mutations predicted to affect the structure of the protein are phenylalanine to valine (Y43V) and lysine to asparagine (K216N) as shown by the trajectory run in molecular dynamics studies. The random transition of the protein structures over the simulation period caused by these mutations hints at how the native state is distorted which could lead to the loss of structural stability and functionality of the nicotinic acetylcholine receptors subunit α-3 protein. Based on this work, we propose that the nsSNP with SNP id of rs75495285 and rs76821682 will have comparatively more deleterious effects than the other predicted mutations in destabilizing the protein structure.
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Acknowledgments
The authors wish to thank the Management, Principal, Director and Head of the Department of the Siddaganga Institute of Technology, Tumkur, and KLE Dr. MSS CET, Belgaum. The authors also thank KBITS for providing computational resources to carry out this study.
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Chandramohan, V., Nagaraju, N., Rathod, S. et al. Identification of Deleterious SNPs and Their Effects on Structural Level in CHRNA3 Gene. Biochem Genet 53, 159–168 (2015). https://doi.org/10.1007/s10528-015-9676-y
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DOI: https://doi.org/10.1007/s10528-015-9676-y