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Exploring non-coding genetic variability in ACE2: Functional annotation and in vitro validation of regulatory variants.

Authors :
Giovannetti A
Lazzari S
Mangoni M
Traversa A
Mazza T
Parisi C
Caputo V
Source :
Gene [Gene] 2024 Jul 15; Vol. 915, pp. 148422. Date of Electronic Publication: 2024 Apr 02.
Publication Year :
2024

Abstract

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 Angiotensin Converting Enzyme 2 (ACE2) 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 ACE2, particularly in its enhancers, promoters, and 3' untranslated regions (UTRs). We found preliminary evidence supporting the regulatory impact of some of these variants on ACE2 expression. Our detailed examination of two SNVs, rs147718775 and rs140394675, in the ACE2 promoter revealed that these co-occurring SNVs, when mutated, significantly enhance promoter activity, suggesting a possible increase in specific ACE2 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.<br />Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.<br /> (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1879-0038
Volume :
915
Database :
MEDLINE
Journal :
Gene
Publication Type :
Academic Journal
Accession number :
38570058
Full Text :
https://doi.org/10.1016/j.gene.2024.148422