In the early, online edition of the Proceedings of the National Academy of Sciences, researchers from the UK and Australia explore associations between rare variants in the gene ERAP1 and an inflammatory spinal arthritis condition called ankylosing spondylitis. By tapping into data for 213 individuals with ankylosing spondylitis and their family members, as well as 46 control individuals with rheumatoid arthritis, the team defined four common haplotypes for variants in and around ERAP1 and compared their frequency in affected and unaffected individuals. Based on their results, the study's authors conclude that "it is common variants in ERAP1 that are mainly responsible for protection/susceptibility in [ankylosing spondylitis] rather than rare ERAP1 variants and/or unusual combinations of ERAP1 variants."
A Harvard- and Imperial College London-led team takes a look at the antigens produced by the respiratory pathogen Streptococcus pneumoniae using pangenome-wide proteomic data. With a custom proteomic array representing thousands of pneumococcal proteins designed with genomic clues from more than 600 nasopharyngeal carriage pneumococcal isolates, the researchers tested blood sera from almost three dozen healthy Americans, narrowing in on 208 antibody-binding targets produced by the pathogen. They note that more than 100 variants fell in a handful of surface or metalloprotease enzyme proteins, while other antigen-affecting variants occurred in conserved proteins. "[S]ome variable antigens rapidly diversified through mechanisms including homologous recombination, mobile genetic element transmission, and phase variation," the authors write. "Other antigens were conserved across the population and may be better candidates for simple vaccine formulations."
Finally, an international team led by investigators at Columbia University describes activating VAV1 alterations that are recurrent in peripheral T-cell lymphoma. The researchers relied on RNA sequencing data for samples from 154 individuals with peripheral T-cell lymphoma, uncovering recurrent mutations and translocations in genes that are known to occur in various sub-types of the disease. But their analyses also unearthed several fusions or mutations involving the guanine exchange factor VAV1 — changes that also turned up in a few more tumors when they considered genomic data for another 126 peripheral T-cell lymphoma cases.