In PLOS Genetics, researchers from Columbia University, Baylor College of Medicine, and other centers in the US search for variants that modify the effects of ABCA4 gene mutations behind diverse eye conditions known as ABCA4/Stargardt disease, which can lead to late-onset macular degeneration, severe retinal degeneration at a relatively young age, and phenotypes in between. The team set out to find potential trans-modifiers influencing these phenotypes at unrelated loci with exome sequences for 622 ABCA4 disease patients, focusing on rare and common variants in seven retinal disease-related genes. The authors flagged rare ROM1 gene variants and a common PRPH2 gene haplotype that appeared to influence disease risk and subtype, respectively, validating the results using data from other ABCA4 patients. "By describing trans-modifiers in a significant fraction of Stargardt/ABCA4 disease, this study adds to the explanation of an unusually complex genetic background," they write, adding that the work "establishes a clear association between ABCA4 and PRPH2/ROM1 variation in disease."
A team from the Dana-Farber Cancer Institute, Harvard University, and elsewhere describes transcriptomic features in small, pathogenic polyomaviruses (PyV) for a paper in PLOS Pathogens. The researchers put together a detailed transcriptome for a human pathogen polyomavirus known as BK (BKPyV), along with a polyomavirus known as simian virus 40, tapping into available short- and long-read RNA sequence profiles for eight human and non-human polyomaviruses. "We identify pervasive wraparound transcription in PyV, wherein transcription runs through the polyA site and circles the genome multiple times," they write, adding that their comparative analyses "identify novel, conserved transcripts that increase PyV coding capacity."
For a paper in PLOS Neglected Tropical Diseases, investigators in the UK, Australia, and Papua New Guinea present findings from a genome sequencing analysis of Salmonella enterica serovar Typhi (S. Typhi) populations found in Papua New Guinea over three decades. The team teased out S. Typhi population structure based on new and previously published whole-genome sequences for dozens of isolates collected in Papua New Guinea from 1980 to 2010, demonstrating that an S. Typhi genotype called 2.1.7 that arose on the Indonesian archipelago has come to predominate in Papua New Guinea. More broadly, the authors note, the S. Typhi population structure tends to be genetically homogeneous and appears to be sensitive to available antibiotic-based typhoid treatments. Even so, they argue that "[r]outine molecular surveillance is necessary to monitor for introduced or emerging [antimicrobial resistance] to inform treatment guidelines and intervention strategies."