In PLOS Genetics, researchers from the University of Bern, University of Leipzig, and elsewhere describe a RAPGEF6 gene insertion with apparent ties to hereditary forms of a respiratory disease called laryngeal paralysis in Miniature Bull Terriers. Starting with a genome-wide association study involving dozens of Miniature Bull Terriers with or without the with the airway obstruction disease, the team focused in on the region in and around the chromosome 11 site that was refined with haplotype analyses and genome sequences from almost 600 more Miniature Bull Terriers. The search led to a 36 base pair insertion in an exon of RAPGEF6 that turned up in 15 affected or unaffected terriers, but was not found in sequences from more than 1,000 dogs from other breeds. "Our results suggest an important role of RAPGEF6 in laryngeal nerve function and provide new clues to its physiological significance," the authors write.
A team from Zimbabwe and South Africa search for inherited contributors to colorectal cancer risk in populations from Zimbabwe for a paper in PLOS One, since CRC cases in sub-Saharan often occur in individuals under 40-years-old. Along with analyses focused on profiling mismatch repair and microsatellite stability patterns in the tumors, the researchers used multiplex ligation-dependent probe amplification and panel sequencing to search for germline risk variants in 90 individuals diagnosed with CRC in Harare from late 2012 to 2015, including 20 patients under 40. The authors tracked down Lynch syndrome-related alterations in one in 30 CRC patients, but conclude that "the majority of colorectal cancers in young people in Zimbabwe, and probably sub-Saharan Africa, are not due to Lynch syndrome."
Investigators in the Netherlands and Norway present findings from a metagenomics-based search for viral contributors to chronic obstructive pulmonary disease for another PLOS One paper. With metagenomic sequencing, the team searched for DNA and RNA virus sequences in almost 90 nasopharyngeal swab samples from 63 Norwegians participating in the Bergen COPD Exacerbation Study, comparing the approach with a quantitative PCR test targeting respiratory viruses. The sequencing approach unearthed potential viral contributors to COPD in 24 of the 88 samples, with sensitivity and specificity that was on par with that offered by more conventional qPCR approaches, the authors report, and pointed to a shift in the proportion of bacteria-infecting viruses in viral communities containing apparent pathogens.