Single nucleotide polymorphisms (SNPs) play a significant role in differences in individual’s susceptibility to diseases, and it is imperative to differentiate potentially harmful SNPs from neutral ones. Defensins are small cationic antimicrobial peptides that serve as antimicrobial and immunomodulatory molecules, and SNPs in β-defensin 1 (DEFB1 gene) have been associated with several diseases. In this study, we have determined deleterious SNPs of the DEFB1 gene that can affect the susceptibility to diseases by using different computational methods. Non-synonymous SNPs (nsSNPs) of the DEFB1 gene that have the ability to affect protein structure and functions were determined by several in silico tools—SIFT, PolyPhen v2, PROVEAN, SNAP, PhD-SNP, and SNPs&GO. Then, nsSNPs identified to be potentially deleterious were further analyzed by I-Mutant and ConSurf. Post-translational modifications mediated by nsSNPs were predicted by ModPred, and gene-gene interaction was studied by GeneMANIA. Finally, nsSNPs were submitted to Project HOPE analysis. Ten nsSNPs of the DEFB1 gene were found to be potentially deleterious: rs1800968, rs55874920, rs56270143, rs140503947, rs145468425, rs146603349, rs199581284, rs201260899, rs371897938, rs376876621. I-Mutant server showed that nsSNPs rs140503947 and rs146603349 decreased stability of the protein, and ConSurf analysis revealed that SNPs were located in conserved regions. The physiochemical properties of the polymorphic amino acid residues and their effect on structure were determined by Project HOPE. This study has determined high-risk deleterious nsSNPs of β-defensin 1 and could increase the knowledge of nsSNPs towards the impact of mutations on structure and functions mediated by β-defensin 1 protein.

中文翻译：

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人 DEFB1 基因非同义单核苷酸多态性的计算机模拟分析

单核苷酸多态性 (SNP) 在个体对疾病易感性的差异中起着重要作用，因此区分潜在有害的 SNP 和中性 SNP 势在必行。防御素是小的阳离子抗菌肽，可作为抗菌和免疫调节分子，β-防御素 1（DEFB1 基因）中的 SNP 与多种疾病有关。在这项研究中，我们通过使用不同的计算方法确定了可能影响疾病易感性的 DEFB1 基因的有害 SNP。具有影响蛋白质结构和功能能力的 DEFB1 基因的非同义 SNP (nsSNP) 由几种计算机工具确定 - SIFT、PolyPhen v2、PROVEAN、SNAP、PhD-SNP 和 SNPs&GO。然后，I-Mutant 和 ConSurf 进一步分析了被鉴定为潜在有害的 nsSNP。由 nsSNPs 介导的翻译后修饰由 ModPred 预测，基因-基因相互作用由 GeneMANIA 研究。最后，将 nsSNP 提交给 Project HOPE 分析。发现 DEFB1 基因的 10 个 nsSNP 具有潜在有害性：rs1800968、rs55874920、rs56270143、rs140503947、rs145468425、rs146603349、rs199677rs3,4967rs28,4961618rs2861618rs8 I-Mutant 服务器显示nsSNPs rs140503947 和rs146603349 降低了蛋白质的稳定性，ConSurf 分析显示SNPs 位于保守区域。多态性氨基酸残基的理化性质及其对结构的影响由 Project HOPE 确定。