Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Laboratory for Molecular Biomedicine, Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Infect Genet Evol. 2020 Oct;84:104498. doi: 10.1016/j.meegid.2020.104498. Epub 2020 Aug 7.
New coronavirus SARS-CoV-2 is capable to infect humans and cause a novel disease COVID-19. Aiming to understand a host genetic component of COVID-19, we focused on variants in genes encoding proteases and genes involved in innate immunity that could be important for susceptibility and resistance to SARS-CoV-2 infection. Analysis of sequence data of coding regions of FURIN, PLG, PRSS1, TMPRSS11a, MBL2 and OAS1 genes in 143 unrelated individuals from Serbian population identified 22 variants with potential functional effect. In silico analyses (PolyPhen-2, SIFT, MutPred2 and Swiss-Pdb Viewer) predicted that 10 variants could impact the structure and/or function of proteins. These protein-altering variants (p.Gly146Ser in FURIN; p.Arg261His and p.Ala494Val in PLG; p.Asn54Lys in PRSS1; p.Arg52Cys, p.Gly54Asp and p.Gly57Glu in MBL2; p.Arg47Gln, p.Ile99Val and p.Arg130His in OAS1) may have predictive value for inter-individual differences in the response to the SARS-CoV-2 infection. Next, we performed comparative population analysis for the same variants using extracted data from the 1000 Genomes project. Population genetic variability was assessed using delta MAF and Fst statistics. Our study pointed to 7 variants in PLG, TMPRSS11a, MBL2 and OAS1 genes with noticeable divergence in allelic frequencies between populations worldwide. Three of them, all in MBL2 gene, were predicted to be damaging, making them the most promising population-specific markers related to SARS-CoV-2 infection. Comparing allelic frequencies between Serbian and other populations, we found that the highest level of genetic divergence related to selected loci was observed with African, followed by East Asian, Central and South American and South Asian populations. When compared with European populations, the highest divergence was observed with Italian population. In conclusion, we identified 4 variants in genes encoding proteases (FURIN, PLG and PRSS1) and 6 in genes involved in the innate immunity (MBL2 and OAS1) that might be relevant for the host response to SARS-CoV-2 infection.
新型冠状病毒 SARS-CoV-2 能够感染人类并引发新型疾病 COVID-19。为了了解 COVID-19 的宿主遗传成分，我们专注于编码蛋白酶和先天免疫基因中的变异，这些变异可能对 SARS-CoV-2 感染的易感性和抵抗力很重要。对来自塞尔维亚人群的 143 个无关个体的 FURIN、PLG、PRSS1、TMPRSS11a、MBL2 和 OAS1 基因编码区的序列数据进行分析，确定了 22 个具有潜在功能影响的变异。在计算机分析（PolyPhen-2、SIFT、MutPred2 和 Swiss-Pdb Viewer）中，预测有 10 个变异可能影响蛋白质的结构和/或功能。这些改变蛋白质的变异（FURIN 中的 p.Gly146Ser；PLG 中的 p.Arg261His 和 p.Ala494Val；PRSS1 中的 p.Asn54Lys；MBL2 中的 p.Arg52Cys、p.Gly54Asp 和 p.Gly57Glu；OAS1 中的 p.Arg47Gln、p.Ile99Val 和 p.Arg130His）可能对 SARS-CoV-2 感染的个体间反应差异具有预测价值。接下来，我们使用 1000 基因组计划中提取的数据，对相同的变异进行了比较的人群分析。使用 delta MAF 和 Fst 统计数据评估了种群遗传变异性。我们的研究指出，PLG、TMPRSS11a、MBL2 和 OAS1 基因中的 7 个变异在全球人群中的等位基因频率存在显著差异。其中 3 个变异（均在 MBL2 基因中）被预测为有害，使其成为与 SARS-CoV-2 感染最相关的最有前途的群体特异性标记。比较塞尔维亚和其他人群的等位基因频率，我们发现与选定基因座相关的遗传分化水平最高的是非洲人群，其次是东亚、中美洲和南美洲以及南亚人群。与欧洲人群相比，与意大利人群的遗传分化水平最高。总之，我们确定了编码蛋白酶（FURIN、PLG 和 PRSS1）的 4 个基因和参与先天免疫的 6 个基因（MBL2 和 OAS1）中的 4 个变异，这些变异可能与宿主对 SARS-CoV-2 感染的反应有关。
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