PloS one
Whole-exome sequencing identifies a missense variant in the cytoskeletal gene SVIL implicating actin remodeling in COVID-19 severity in a Pakistani cohort
Door Sadiq M, Wasim B, Khatoon A en 4 anderen.
Inhoud in het Engels
Abstract
Background
The current study investigated host genetic associations with disease severity in COVID-19 patients of South Asian origin and explored its molecular basis.
Methods
Covid-19 patients were stratified into disease severity groups based on the clinical and radiographic findings. Genomic DNA was extracted from peripheral blood samples. A two-step discovery and validation approach was utilized for genetic analysis. Whole-exome sequencing (WES) based variant prioritization was performed in a discovery cohort of severe disease patients followed by validation in an independent cohort. Bioinformatics analysis including data alignment, and annotation to the GRCh38 human reference genome was done by Ensembl VEP software. WES filtration pipeline utilizing predicted pathogenicity and population allele frequencies focused on the low-frequency and rare variants to filter out the variants of concern. Computational predictive tools and simulations were utilized for the structural and functional analysis of the identified high-risk SNP. Statistical analyses were done by SPSS version 24 and GraphPad Prism version 10.