The surge in human whole-genome sequencing data has facilitated the study of non-coding region variations, yet understanding their biological significance remains a challenge. We used a computational workflow to assess the regulatory potential of non-coding variants, with a particular focus on the ( gene. This gene is crucial in physiological processes and serves as the entry point for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing coronavirus disease 19 (COVID-19). In our analysis, using data from the gnomAD population database and functional annotation, we identified 17 significant Single Nucleotide Variants (SNVs) in , particularly in its enhancers, promoters, and 3′ untranslated regions (UTRs). We found preliminary evidence supporting the regulatory impact of some of these variants on expression. Our detailed examination of two SNVs, rs147718775 and rs140394675, in the promoter revealed that these co-occurring SNVs, when mutated, significantly enhance promoter activity, suggesting a possible increase in specific isoform expression. This method proves effective in identifying and interpreting impactful non-coding variants, aiding in further studies and enhancing understanding of molecular bases of monogenic and complex traits.

中文翻译：

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探索 ACE2 中的非编码遗传变异：调节变异的功能注释和体外验证

人类全基因组测序数据的激增促进了非编码区变异的研究，但了解其生物学意义仍然是一个挑战。我们使用计算工作流程来评估非编码变体的调控潜力，特别关注 ( 基因)。该基因在生理过程中至关重要，是严重急性呼吸综合征冠状病毒 2 (SARS-CoV- 2) 引起冠状病毒疾病 19 (COVID-19) 的病毒。在我们的分析中，使用 gnomAD 群体数据库的数据和功能注释，我们鉴定了 17 个显着的单核苷酸变异体 (SNV)，特别是其增强子、启动子和3'非翻译区（UTR）。我们发现了支持其中一些变体对表达的调节影响的初步证据。我们对启动子中的两个 SNV rs147718775 和 rs140394675 的详细检查表明，这些共存的 SNV 在突变时显着增强启动子活性，表明特定亚型表达可能增加。该方法被证明可以有效识别和解释有影响力的非编码变异，有助于进一步研究并增强对单基因和复杂性状分子基础的理解。