人类AGT基因单核苷酸多态性的计算分析

Mohammed Youssif Mohammed, Afra M. Al Bkrye, H. A. Elnasri, M. A. Khaier
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引用次数: 0

摘要

背景:AGT基因是负责调节一种叫做血管紧张素原的蛋白质的基因,这种蛋白质调节血压和平衡体内的液体。高血压的发生是由多种原因引起的,其中之一是AGT基因缺陷。高血压通常没有症状。然而,它是心脏病、中风、肾衰竭和眼睛问题的主要危险因素。目的:在本研究中,我们使用软件对基因进行分析,使用不同的软件和统计表示,并检测导致疾病的snp。材料和方法:本研究使用多种软件工具对NCBI网站检索到的nssnp进行分析。这些软件包括SIFT, I-mutant, polyphen2, PHD SNP和SNP& Go, Projecthop和GeneMANIA。结果:在172个nssnp中,只有46个nssnp是有害的,而126个nssnp是可耐受的。2例为良性,11例为可能损伤,33例为可能被polyphen2损伤。使用Provean, 19个nssnp是中性的,27个是有害的。在PHD-SNP软件中,20个nssnp与疾病相关,18个为中性。使用SNP & Go软件检查SNP,结果显示32个中性nssnp和14个nssnp为疾病相关变异。使用I-Mutant软件,13个nsSNPs增加了蛋白质的稳定性,33个降低了蛋白质的稳定性。结论:利用生物信息学和计算方法对AGT基因进行了广泛的功能和结构分析,以预测潜在的破坏性和有害的非单核苷酸多态性。本研究从172个nssnp中鉴定出14个高置信度的破坏性nssnp。尽管生物信息学工具有其局限性,但本研究的结果可能有助于未来进一步开展基于人群的研究活动和开发准确的药物。
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Data Analysis of Single Nucleotide Polymorphism in Human AGT Gene Using Computational Approach
Background: The AGT gene is gene responsible for regulation of protein called angiotensinogen which regulates blood pressure and balances fluids in the body. Hypertension happens due to many causes one of this is the defect in AGT gene. Hypertension usually has no symptoms. However, it is a major risk factor for heart diseases, stroke, kidney failure, and eye problems. Objectives: in this study we use software to analyze the gene using different software and represented statistically and to detect the SNPs that can cause the disease. Material and Method: In this analysis using many software tools that can analyze the nsSNPs retrieved from NCBI website. These software include SIFT, I-mutant, Polyphen-2, PHD SNP and SNP& Go, Projecthop and GeneMANIA. Results: The study showed that from 172 nsSNPs only 46 nsSNPs were deleterious while 126 were tolerated using SIFT. Two were benign, 11 were possibly damaging and 33 were probably damaging by Polyphen-2. Using Provean, 19 nsSNPs were neutral and 27 were deleterious. For PHD-SNP software 20 nsSNPs were disease related and 18 were neutral. Also SNPs were checked using SNP & Go software that showed 32 neutral nsSNPs and 14 nsSNPs were disease associated variants. Using I-Mutant software 13 nsSNPs increase the stability of the protein and 33 decrease the protein stability. Conclusions: In conclusion, extensive functional and structural analyses are carried out to predict potentially damaging and deleterious nsSNPs of AGT gene using bioinformatics and computational methods. In the study, 14 high confidence damaging nsSNPs are identified from 172 nsSNPs. Although bioinformatics tools have their limitations, the results from the present study may be convenient in future for further population based research activities and towards development of accuracy medicines.
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