Department of Biotechnology, K L University, Andhra Pradesh, India.
Gene. 2013 Jan 10;512(2):429-37. doi: 10.1016/j.gene.2012.08.026. Epub 2012 Aug 30.
Non-synonymous single nucleotide polymorphisms (nsSNPs) are considered as biomarkers to disease susceptibility. In the present study, nsSNPs in CLU, PICALM and BIN1 genes were screened for their functional impact on concerned proteins and their plausible role in Alzheimer disease (AD) susceptibility. Initially, SNPs were retrieved from dbSNP database, followed by identification of potentially deleterious nsSNPs and prediction of their effect on proteins by PolyPhen and SIFT. Protein stability and the probability of mutation occurrence were predicted using I-Mutant and PANTHER respectively. SNPs3D and FASTSNP were used for the functional analysis of nsSNPs. The functional impact on the 3D structure of proteins was evaluated by SWISSPDB viewer and NOMAD-Ref server. On analysis, 3 nsSNPs with IDs rs12800974 (T158P) of PICALM and rs11554585 (R397C) and rs11554585 (N106D) of BIN1 were predicted to be functionally significant with higher scores of I-Mutant, SIFT, PolyPhen, PANTHER, FASTSNP and SNPs3D. The mutant models of these nsSNPs also showed very high energies and RMSD values compared to their native structures. Current study proposes that the three nsSNPs identified in this study constitute a unique resource of potential genetic factors for AD susceptibility.
非 synonymous单核苷酸多态性 (nsSNPs) 被认为是疾病易感性的生物标志物。在本研究中,筛选了 CLU、PICALM 和 BIN1 基因中的 nsSNPs,以研究它们对相关蛋白的功能影响及其在阿尔茨海默病 (AD) 易感性中的可能作用。最初,从 dbSNP 数据库中检索 SNPs,然后识别潜在的有害 nsSNPs,并通过 PolyPhen 和 SIFT 预测它们对蛋白质的影响。使用 I-Mutant 和 PANTHER 分别预测蛋白质稳定性和突变发生的概率。使用 SNPs3D 和 FASTSNP 对 nsSNPs 进行功能分析。使用 SWISSPDB 查看器和 NOMAD-Ref 服务器评估对蛋白质 3D 结构的功能影响。分析表明,PICALM 的 ID rs12800974(T158P)、BIN1 的 rs11554585(R397C)和 rs11554585(N106D) 这 3 个 SNP 被预测具有功能意义,其 I-Mutant、SIFT、PolyPhen、PANTHER、FASTSNP 和 SNPs3D 的评分较高。与天然结构相比,这些 nsSNPs 的突变模型的能量和 RMSD 值也非常高。本研究提出,本研究中鉴定的这三个 nsSNPs 构成了 AD 易感性潜在遗传因素的独特资源。