Identification of regulatory variants associated with genetic susceptibility to meningococcal disease

Non-coding genetic variants play an important role in driving susceptibility to complex diseases but their characterization remains challenging. Here, we employed a novel approach to interrogate the genetic risk of such polymorphisms in a more systematic way by targeting specific regulatory regions relevant for the phenotype studied. We applied this method to meningococcal disease susceptibility, using the DNA binding pattern of RELA - a NF-kB subunit, master regulator of the response to infection - under bacterial stimuli in nasopharyngeal epithelial cells. We designed a custom panel to cover these RELA binding sites and used it for targeted sequencing in cases and controls. Variant calling and association analysis were performed followed by validation of candidate polymorphisms by genotyping in three independent cohorts. We identified two new polymorphisms, rs4823231 and rs11913168, showing signs of association with meningococcal disease susceptibility. In addition, using our genomic data as well as publicly available resources, we found evidences for these SNPs to have potential regulatory effects on ATXN10 and LIF genes respectively. The variants and related candidate genes are relevant for infectious diseases and may have important contribution for meningococcal disease pathology. Finally, we described a novel genetic association approach that could be applied to other phenotypes

Plasma lipid profiles discriminate bacterial from viral infection in febrile children

Fever is the most common reason that children present to Emergency Departments. Clinical signs and symptoms suggestive of bacterial infection ar

The effect of cutting on the proportions of white clover in mixtures

In two experiments with ryegrass/white clover mixtures, the proportion of clover was measured before and after cuts which removed 8-75% of above-ground biomass. Cutting was found to reduce the proportion of clover leaf area in the crop in both experiments, sometimes by as much as two-thirds, and the proportion of clover dry weight, by up to half, in one of them. That is, the harvested material contained a greater proportion of clover than did the sward before the cut. This disproportionate removal of clover was due to clover having a greater proportion of its leaf near the top of the canopy than grass. It showed that preferential removal of clover occurs as a result of the purely passive selection by a mower, not only as a result of grazing by animals which may be capable of active as well as passive selection. Despite the disadvantage to clover of losing more of its leaf area than grass, and in some cases more of its dry weight also, when the mixture was cut, the clover content of the sward did not decrease during the growing season as a whole. This was because, where no nitrogen fertilizer was applied, clover had a greater relative growth rate (RGR) than its companion grass during the growth periods between cuts and this increased its percentage of the mixture. Even where nitrogen was applied, clover equalled the RGR of grass and maintained its proportion of the crop, except in one instance