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

Inter-annual depth-dependent toxicity and bioaccumulation of cadmium in marine benthic protist communities

The toxicity and bioaccumulation of cadmium in a marine benthic protist community were examined at different depths within the sediment. For this purpose, sediment-water microcosms with 1000 μgCd dm−3 of the pollutant were used in two assays. The addition of cadmium caused a significant reduction in protist density, number of species and biomass. There was also a decrease in these three parameters with depth. During the treatment the density of protist groups was strongly depth-dependent. The dominant groups of protists at the different depths during the assay were also considered. The most dominant protist group in terms of density were the heterotrophic flagellates, both in the control and in the treatment with cadmium. In the treatments with cadmium, these were followed by ciliates and by dinoflagellates in both assays. In the control, all protist groups were present during the assay, whereas in the treatments with cadmium, autotrophic flagellates, diatoms and sarcodines were found in reduced proportion or not at all. Cadmium bioaccumulation increased towards the end of the assay. At any time during the assay, the proportion of cadmium bioaccumulated was an increasing function of depth