大西洋鲑鱼一组免疫相关表达序列标签(EST)中的单核苷酸多态性(SNP)挖掘及其对三维蛋白质结构预测的影响。
Single-Nucleotide Polymorphisms (SNP) Mining and Their Effect on the Tridimensional Protein Structure Prediction in a Set of Immunity-Related Expressed Sequence Tags (EST) in Atlantic Salmon ().
作者信息
Vallejos-Vidal Eva, Reyes-Cerpa Sebastián, Rivas-Pardo Jaime Andrés, Maisey Kevin, Yáñez José M, Valenzuela Hector, Cea Pablo A, Castro-Fernandez Victor, Tort Lluis, Sandino Ana M, Imarai Mónica, Reyes-López Felipe E
机构信息
Department of Cell Biology, Physiology and Immunology, Faculty of Biosciences, Universitat Autònoma de Barcelona, Barcelona, Spain.
Centro de Genómica y Bioinformática, Facultad de Ciencias, Universidad Mayor, Santiago, Chile.
出版信息
Front Genet. 2020 Feb 27;10:1406. doi: 10.3389/fgene.2019.01406. eCollection 2019.
Single-nucleotide polymorphisms (SNPs) are single genetic code variations considered one of the most common forms of nucleotide modifications. Such SNPs can be located in genes associated to immune response and, therefore, they may have direct implications over the phenotype of susceptibility to infections affecting the productive sector. In this study, a set of immune-related genes ( [], integrin β2 (itβ2, also named ), [], [], []) were analyzed to identify SNPs by data mining. These genes were chosen based on their previously reported expression on infectious pancreatic necrosis virus (IPNV)-infected Atlantic salmon phenotype. The available EST sequences for these genes were obtained from the Unigene database. Twenty-eight SNPs were found in the genes evaluated and identified most of them as transition base changes. The effect of the SNPs located on the 5'-untranslated region (UTR) or 3'-UTR upon transcription factor binding sites and alternative splicing regulatory motifs was assessed and ranked with a low-medium predicted FASTSNP score risk. Synonymous SNPs were found on (c.2275G > A), (c.558G > A), and (c.1950C > T) with low FASTSNP predicted score risk. The difference in the relative synonymous codon usage (RSCU) value between the variant codons and the wild-type codon (ΔRSCU) showed one negative ( c.1950C > T) and two positive ΔRSCU values ( c.2275G > A; c.558G > A), suggesting that these synonymous SNPs (sSNPs) may be associated to differences in the local rate of elongation. Nonsynonymous SNPs (nsSNPs) in the translatable gene region were ranked, using SIFT and POLYPHEN web-tools, with the second highest (c.205A > G; c484T > C) and the highest (c.499T > C; c.769A > C) predicted score risk possible. Using homology modeling to predict the effect of these nonsynonymous SNPs, the most relevant nucleotide changes for were observed for the nsSNPs c.205A > G, c484T > C, and c.769A > C. Molecular dynamics was assessed to analyze if these GSTO-1 variants have significant differences in their conformational dynamics, suggesting these SNPs could have allosteric effects modulating its catalysis. Altogether, these results suggest that candidate SNPs identified may play a crucial potential role in the immune response of Atlantic salmon.
单核苷酸多态性(SNPs)是单个遗传密码变异,被认为是核苷酸修饰最常见的形式之一。此类单核苷酸多态性可位于与免疫反应相关的基因中,因此,它们可能对影响生产部门的感染易感性表型有直接影响。在本研究中,通过数据挖掘分析了一组免疫相关基因([]、整合素β2(itβ2,也称为[])、[]、[]、[])以鉴定单核苷酸多态性。选择这些基因是基于它们先前报道的在感染传染性胰腺坏死病毒(IPNV)的大西洋鲑表型中的表达情况。这些基因的可用EST序列从Unigene数据库中获得。在评估的基因中发现了28个单核苷酸多态性,并且鉴定出其中大多数为转换碱基变化。评估了位于5'-非翻译区(UTR)或3'-UTR上的单核苷酸多态性对转录因子结合位点和可变剪接调控基序的影响,并以中低预测FASTSNP评分风险进行排名。在(c.2275G>A)、(c.558G>A)和(c.1950C>T)上发现了同义单核苷酸多态性,预测FASTSNP评分风险较低。变异密码子与野生型密码子之间的相对同义密码子使用(RSCU)值差异(ΔRSCU)显示一个为负(c.1950C>T),两个为正ΔRSCU值(c.2275G>A;c.558G>A),表明这些同义单核苷酸多态性(sSNPs)可能与局部延伸速率的差异有关。使用SIFT和POLYPHEN网络工具对可翻译基因区域中的非同义单核苷酸多态性(nsSNPs)进行排名,预测评分风险分别为第二高(c.205A>G;c484T>C)和最高(c.499T>C;c.769A>C)。使用同源建模预测这些非同义单核苷酸多态性的影响,观察到对于nsSNPs c.205A>G、c484T>C和c.769A>C,对[]而言最相关的核苷酸变化。评估分子动力学以分析这些GSTO-1变体在其构象动力学上是否有显著差异,表明这些单核苷酸多态性可能具有变构效应来调节其催化作用。总之,这些结果表明所鉴定的候选单核苷酸多态性可能在大西洋鲑的免疫反应中发挥关键的潜在作用。
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