In-silico analysis of deleterious non-synonymous SNPs in the human AVPR1a gene linked to autism.

IF 3.5 2区 生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Md Delowar Kobir Jibon, Md Asadul Islam, Md Eram Hosen, Md Omar Faruqe, Rashed Zaman, Uzzal Kumar Acharjee, Biswanath Sikdar, Yewulsew Kebede Tiruneh, Md Khalekuzzaman, Motasim Jawi, Magdi E A Zaki
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Abstract

Single nucleotide polymorphisms are the most prevalent type of DNA variation occurring at a single nucleotide within the genomic sequence. The AVPR1a gene exhibits genetic polymorphism and is linked to neurological and developmental problems, including autism spectrum disorder. Due to the difficulties of studying all non-synonymous single nucleotide polymorphisms (nsSNPs) of the AVPR1a gene in the general population, our goal is to use a computational approach to identify the most detrimental nsSNPs of the AVPR1a gene. We employed several bioinformatics tools, such as SNPnexus, PROVEAN, PANTHER, PhD-SNP, SNP & GO, and I-Mutant2.0, to detect the 23 most detrimental mutants (R85H, D202N, E54G, H92P, D148Y, C203G, V297M, D148V, S182N, Q108L, R149C, G212V, M145T, G212S, Y140S, F207V, Q108H, W219G, R284W, L93F, P156R, F136C, P107L). Later, we used other bioinformatics tools to perform domain and conservation analysis. We analyzed the consequences of high‑risk nsSNPs on active sites, post-translational modification (PTM) sites, and their functional effects on protein stability. 3D modeling, structure validation, protein-ligand binding affinity prediction, and Protein-protein docking were conducted to verify the presence of five significant substitutions (R284W, Y140S, P107L, R149C, and F207V) and explore the modifications induced due to these mutants. These non-synonymous single nucleotide polymorphisms can potentially be the focus of future investigations into various illnesses caused by AVPR1a malfunction. Employing in-silico methodologies to evaluate AVPR1a gene variants will facilitate the coordination of extensive investigations and the formulation of specific therapeutic approaches for diseases associated with these variations.

与自闭症相关的人类AVPR1a基因中有害的非同义snp的计算机分析。
单核苷酸多态性是基因组序列中发生在单个核苷酸上的最普遍的DNA变异类型。AVPR1a基因表现出遗传多态性,与神经和发育问题有关,包括自闭症谱系障碍。由于在普通人群中研究AVPR1a基因的所有非同义单核苷酸多态性(nsSNPs)存在困难,我们的目标是使用计算方法来识别AVPR1a基因中最有害的nsSNPs。采用SNPnexus、PROVEAN、PANTHER、ph -SNP、SNP & GO和I-Mutant2.0等生物信息学工具,检测了23个最有害的突变体(R85H、D202N、E54G、H92P、D148Y、C203G、V297M、D148V、S182N、Q108L、R149C、G212V、M145T、G212S、Y140S、F207V、Q108H、W219G、R284W、L93F、P156R、F136C、P107L)。随后,我们使用其他生物信息学工具进行域和保守性分析。我们分析了高风险nssnp对活性位点、翻译后修饰(PTM)位点的影响,以及它们对蛋白质稳定性的功能影响。通过三维建模、结构验证、蛋白-配体结合亲和预测、蛋白-蛋白对接,验证了5个重要的取代位点(R284W、Y140S、P107L、R149C和F207V)的存在,并探讨了这些突变体引起的修饰。这些非同义的单核苷酸多态性可能是未来研究由AVPR1a功能障碍引起的各种疾病的重点。采用计算机方法评估AVPR1a基因变异将有助于协调广泛的研究和制定与这些变异相关的疾病的特定治疗方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Genomics
BMC Genomics 生物-生物工程与应用微生物
CiteScore
7.40
自引率
4.50%
发文量
769
审稿时长
6.4 months
期刊介绍: BMC Genomics is an open access, peer-reviewed journal that considers articles on all aspects of genome-scale analysis, functional genomics, and proteomics. BMC Genomics is part of the BMC series which publishes subject-specific journals focused on the needs of individual research communities across all areas of biology and medicine. We offer an efficient, fair and friendly peer review service, and are committed to publishing all sound science, provided that there is some advance in knowledge presented by the work.
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