Sabiha Bibi, Bhatti Attya, Roomi Sohaib, John Peter, Ali Johar
Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12 Islamabad, Pakistan.
Healthcare Biotechnology, Atta-ur-Rahman School of Applied Biosciences (ASAB), National University of Sciences and Technology (NUST), H-12 Islamabad, Pakistan.
Genomics. 2021 Jul;113(4):2426-2440. doi: 10.1016/j.ygeno.2021.05.022. Epub 2021 May 21.
Non-synonymous missense SNPs (nsSNPs) in CPE and GNAS genes were investigated computationally. In silico identified nsSNPs were experimentally validated in type II diabetes mellitus (T2DM) in Pakistani Pathan population using next generation sequencing (NGS). Sixty two high-risk nsSNPs in CPE and 44 in GNAS were identified. Only 12 in GNAS were clinically significant. Thirty six high-risk nsSNPs in CPE and 08 clinically significant nsSNPs in GNAS lies in the most conserved regions. I-mutant predicted that nsSNPs decrease the proteins stability and ModPred predicted 20 and 12 post-translational modification sites in CPE and GNAS proteins respectively. Ramachandran plot showed 88.7% residues are in the most favored region of protein models. By experimentation, none of the nsSNPs were found to be associated with T2DM. In conclusion, this study differentiates the deleterious nsSNPs from the neutral ones. Although nsSNPs are not associated with T2DM, they can be targeted in other CPE and GNAS genes related disorders.
对CPE和GNAS基因中的非同义错义单核苷酸多态性（nsSNPs）进行了计算研究。通过计算机鉴定出的nsSNPs，利用下一代测序（NGS）在巴基斯坦帕坦族人群的II型糖尿病（T2DM）中进行了实验验证。在CPE中鉴定出62个高危nsSNPs，在GNAS中鉴定出44个。在GNAS中只有12个具有临床意义。CPE中的36个高危nsSNPs和GNAS中的8个具有临床意义的nsSNPs位于最保守的区域。I-mutant预测nsSNPs会降低蛋白质稳定性，ModPred分别预测CPE和GNAS蛋白质中有20个和12个翻译后修饰位点。拉氏图显示88.7%的残基位于蛋白质模型的最有利区域。通过实验，未发现任何nsSNPs与T2DM相关。总之，本研究区分了有害的nsSNPs和中性的nsSNPs。虽然nsSNPs与T2DM无关，但它们可作为其他与CPE和GNAS基因相关疾病的靶点。
