In PLOS Genetics, researchers from Germany, the UK, Denmark, and elsewhere describe new genes with apparent ties to sporadic thoracic aortic aneurysm and other forms of congenital heart disease (CHD). Using copy number variant data for 7,958 individuals with CHD and nearly 14,000 without, along with de novo variant insights gleaned from almost 2,500 parent-child trios, the team searched for genes with an over-representation of rare alterations in the CHD-affected individuals, focusing in on 14 known and seven new CHD-associated genes. For a subsequent systems-based analysis, the authors incorporated protein interaction network data to identify pertinent pathways related to heart morphogenesis, Notch signaling, DNA repair, and other processes. "This analysis, which is one of the larger meta-analyses of genomic variants in CHD so far, strengthens the disease association of known CHD genes and identifies novel haploinsufficient CHD candidate genes," they write.
For a paper in PLOS Pathogens, a team led by investigators from the Australian Centre for Disease Preparedness flags a handful of microRNAs with altered expression in blood plasma from individuals with COVID-19. Starting with plasma samples collected over time from 10 individuals treated for SARS-CoV-2 infections at a hospital in Melbourne in early 2020, along with samples from as many unaffected, symptom-free individuals who tested negative for COVID-19, the team used small RNA sequencing to find dozens of miRNAs with expression shifts in early-stages of infection and in COVID-19 cases that involved oxygen treatment. From there, they turned to machine learning to whittle that set down to three infection-related miRNAs — a signature that successfully identified SARS-CoV-2 infections in humans and in a ferret model. "[T]his study exemplifies how analysis of miRNA responses to SARS-CoV-2 infection presents novel avenues in the characterization of cellular factors aiding in COVID-19 pathogenesis," they report, adding that the approach "presents novel opportunities for treatment and diagnosis of viral diseases."
Investigators in Cyprus outline mutations found by exome sequencing in individuals with multiple malformation syndrome (MMS) from the Greek-Cypriot population for a study published in PLOS One. By sequencing protein-coding parts of the genome in 100 individuals from 32 MMS-affected families, including 37 individuals with yet-undiagnosed forms of MMS, the team tracked down 17 MMS-related autosomal dominant de novo variants in 14 new or known risk genes that were investigated further in a series of subsequent functional analyses and experiments. "The high diagnostic yield and efficacy of [whole-exome sequencing (WES)] observed in this study suggest that WES could … be considered as a first-tier cost effective diagnostic test over conventional diagnostic approaches for MMS patients when a specific disorder is not suspected," the authors suggest, noting that "the genes in which flagged variants were identified in this study could be added in clinical exome sequencing and related panels for MMS."