In PLOS Genetics, researchers from Israel and the US describe ties between an early-onset dilated cardiomyopathy (DCM) heart condition and a recessive mutation in the protein kinase enzyme-coding gene SPEG, which is enriched in striated muscle tissue. Using clinical data, array-based family linkage and homozygosity mapping, and exome sequencing in an affected Israeli Bedouin family, the team narrowed in on an early-onset DCM-associated autosomal recessive change in the SPEG gene, which it went on to characterize further with CRISPR-Cas9-based gene editing, induced pluripotent stem (iPSC) cell-derived cardiomyocyte experiments, and functional analyses. “We provide a proof-of-concept that in vitro iPSC models that could effectively validate the pathogenicity of novel genetic variants associated with recessively inherited DCM that are otherwise poorly supported by few probands and families,” the authors report.
A University of Southern California team shares findings from an epigenetic analysis of the lung cancer subtype lung adenocarcinoma for another paper in PLOS Genetics. The researchers relied on an updated version of a “Tracing Enhancer Networks using Epigenetic Traits” (TENET) 2.0 tool to analyze sequencing-based chromatin assay and transcriptome data for lung adenocarcinoma cells, comparing them to those in cells from normal lung samples. The approach uncovered more than 32,000 differentially activated enhancers, along with altered transcriptional regulators that they went on to explore with gene silencing and functional experiments. “Identification and characterization of key transcriptional regulators and associated enhancers in lung adenocarcinoma provides important insights into the deregulation of lung adenocarcinoma epigenomes,” they report, “highlighting novel potential targets for clinical intervention.”
For a prospective epidemiological study in PLOS One, investigators from the University of Utah, Salt Lake City’s Primary Children’s Hospital, and Baylor College of Medicine retrace clinical and molecular features of invasive Staphylococcus aureus infections reported in children from Utah between early 2009 and late 2012. The team did multi-locus sequence typing and targeted PCR testing on S. aureus isolates from more than 350 treated for invasive S. aureus infection at hospitals in Utah over four years, identifying half a dozen main clonal complexes and 41 multi-locus sequence types. The authors note that 21 percent of cases were classified as methicillin-resistant S. aureus (MRSA), while the remaining invasive infections involved methicillin-susceptible S. aureus (MSSA) strains. “MSSA was the primary cause of invasive S. aureus infections at our institution throughout the study period,” the authors write, noting that a “limited number of predominant strains accounted for the majority of invasive disease.”