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PLOS Papers on Typhoid Fever Host Genetics, COVID-19-Related RNA Splicing, More

In PLOS Genetics, researchers from Texas A&M University and Colorado State University describe host genetics-related survival differences in mouse models of infection with the Salmonella enterica serovar Typhimurium, which causes typhoid fever. Using nearly three dozen genetically distinct mouse strains from the Collaborative Cross collection, the team tracked clinical features and outcomes in the days following oral infection with S. Typhimurium. Along with lower-than-usual body temperatures and activity levels prior to infection, the authors linked survival to new and known risk loci on chromosomes 1, 2, 4, and 7. "We identified a broad range of outcomes across these different mice, including a group of mice susceptible to lethal infection and a group that survived our [seven] day study," the authors write, noting that the study "defines the utility of exploring how host genetic diversity influences infection outcomes with bacterial pathogens."

For another paper in PLOS Genetics, a team from the Huazhong University of Science and Technology and other centers in China and the US present evidence of altered RNA splicing in lung tissues from nine fatal COVID-19 cases from the initial Wuhan wave and 10 control samples. With a combination of proteomic profiling and transcriptome sequencing, the researchers saw transcript splicing shifts and alternative transcript usage, particularly when it came to genes related to blood coagulation, immune function, and antiviral activity. "[T]he dysregulation of transcripts was strongly correlated with clinical severity of COVID-19, and splice-variants may contribute to unexpected therapeutic activity," they report, noting that "SARS-CoV-2 proteins directly engage host spliceosome to dysregulate essential steps of mature mRNA production and result in widespread dysregulation of cellular function."

Investigators reporting in PLOS One describe apparent genetic ties between intracranial aneurysm and acute ischemic stroke in individuals from Korea, demonstrating with the development of a polygenic risk score (PRS) linked to the risk of both conditions. The team settled on a PRS model for predicting intracranial aneurysm by analyzing weighted PRS models established using data from a prior genome-wide association study that included more than 470 intracranial aneurysm or acute ischemic stroke cases, and nearly 300 unaffected controls, subsequently linking the resulting PRS to elevated risk of acute ischemic stroke as well. Based on these and other results, the authors suggest that intracranial aneurysm and acute ischemic stroke "may have a shared genetic architecture and should be studied further to generate a precision medicine model for use in personalized diagnosis and treatment.

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