Identification of Deleterious SNPs and Their Effects on Structural Level in CHRNA3 Gene

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• 作者：Vivek Chandramohan ; Navya Nagaraju ; Shrikant Rathod ; Anubhav Kaphle…
• 关键词：CHRNA3 ; SIFT ; PredictSNP ; Molecular modeling ; Molecular dynamics
• 刊名：Biochemical Genetics
• 出版年：2015
• 出版时间：August 2015
• 年：2015
• 卷：53
• 期：7-8
• 页码：159-168
• 全文大小：2,747 KB
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• 作者单位：Vivek Chandramohan (1)
  Navya Nagaraju (1)
  Shrikant Rathod (2)
  Anubhav Kaphle (1)
  Uday Muddapur (2)
  
  1. Department of Biotechnology, Siddaganga Institute of Technology, Tumkur, 572013, Karnataka, India
  2. Department of Biotechnology, KLE Dr. MSS CET, Belgaum, India
  
• 刊物类别：Biomedical and Life Sciences
• 刊物主题：Biomedicine
  Human Genetics
  Biochemistry
  Zoology
  Medical Microbiology
  
• 出版者：Springer Netherlands
• ISSN：1573-4927

文摘

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.