Common and Rare 5'UTR Variants Altering Upstream Open Reading Frames in Cardiovascular Genomics
Omar Soukarieh1, Caroline Meguerditchian1, Carole Proust1
1INSERM, Bordeaux Population Health, U1219, Molecular Epidemiology of Vascular and Brain Disorders, University of Bordeaux, Bordeaux, France.
Frontiers in Cardiovascular Medicine
|April 7, 2022
Summary
High-throughput sequencing aids disease gene discovery. This study explores how 5' untranslated region (5'UTR) variants affecting upstream open reading frames (upORFs) contribute to rare and common cardiovascular disorders (CVDs).
Area of Science:
- Genetics and Genomics
- Molecular Biology
- Cardiovascular Research
Background:
- High-throughput sequencing (HTS) enables large-scale genetic variation analysis for disease research.
- Identifying genetic causes of rare (Mendelian) and common (multifactorial) diseases is crucial for molecular diagnosis.
- Non-coding regions, including 5' untranslated regions (5'UTR), are under-explored for disease-causing variants.
Purpose of the Study:
- To review known 5'UTR variants that alter upstream open reading frames (upORFs) and cause rare cardiovascular disorders (CVDs).
- To investigate the potential role of upORF-altering single nucleotide polymorphisms (SNPs) in explaining genome-wide association study (GWAS) signals for common complex CVDs.
Main Methods:
- Review of existing literature on 5'UTR variants, upORFs, and their association with rare cardiovascular diseases.
- Bioinformatic and genetic analysis to assess the candidacy of upORF-associated SNPs for common complex CVDs identified through GWAS.
Main Results:
- Summarizes known 5'UTR variations impacting upORFs and their link to rare cardiovascular disorders.
- Presents an investigation into whether these upORF-altering variants can explain genetic associations found in large-scale studies of common cardiovascular diseases.
Conclusions:
- 5'UTR variants affecting upORFs are implicated in rare cardiovascular diseases.
- These variants represent potential candidates for explaining genetic associations in common complex cardiovascular disorders, warranting further investigation.
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