Exploring non-coding genetic variability in ACE2: Functional annotation and in vitro validation of regulatory
Agnese Giovannetti1, Sara Lazzari2, Manuel Mangoni3
1Clinical Genomics Laboratory, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini, snc, 71013 S. Giovanni Rotondo (FG), Italy.
Gene
|April 3, 2024
Summary
Computational analysis of non-coding variants in the Angiotensin Converting Enzyme 2 (ACE2) gene identified significant Single Nucleotide Variants (SNVs). Some variants, particularly in the ACE2 promoter, enhance gene activity, impacting ACE2 expression and COVID-19 susceptibility.
Area of Science:
- Genomics
- Molecular Biology
- Bioinformatics
Background:
- Human whole-genome sequencing generates vast data, enabling non-coding region variation studies.
- Understanding the biological significance of non-coding variants remains a significant challenge.
- The Angiotensin Converting Enzyme 2 (ACE2) gene is vital for physiological processes and serves as the SARS-CoV-2 entry receptor.
Purpose of the Study:
- To computationally assess the regulatory potential of non-coding variants.
- To identify and interpret impactful non-coding variants in the ACE2 gene.
- To investigate the regulatory impact of specific ACE2 variants on gene expression.
Main Methods:
- Utilized a computational workflow for regulatory potential assessment.
- Analyzed data from the gnomAD population database and functional annotation.
- Focused on Single Nucleotide Variants (SNVs) in ACE2 enhancers, promoters, and 3' untranslated regions (UTRs).
Main Results:
- Identified 17 significant SNVs in the ACE2 gene.
- Found preliminary evidence for the regulatory impact of some variants on ACE2 expression.
- Observed that two specific ACE2 promoter SNVs (rs147718775 and rs140394675) enhance promoter activity when mutated, potentially increasing ACE2 isoform expression.
Conclusions:
- The computational method effectively identifies and interprets impactful non-coding variants.
- Findings contribute to understanding the molecular basis of monogenic and complex traits.
- The study provides insights into ACE2 regulation and its potential role in COVID-19.
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