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

Valor nutritivo da forragem de genótipos de cereais de inverno de duplo propósito Nutritive value of forage of genotypes of double purpose winter cereals

Esta pesquisa foi conduzida com o objetivo de avaliar o valor nutritivo da forragem de 12 genótipos de seis espécies de cereais de inverno de duplo propósito (forragem e grãos), submetidos ao corte, na região da Depressão Central do Rio Grande do Sul. As espécies e genótipos testados foram: trigo (BRS 277, BRS Guatambu, BRS Tarumã, BRS Umbu); aveia-preta (Agro Zebu, UPFA 21 - Moreninha e Comum); aveia-branca (UPF 18); centeio (BR 1 e BRS Serrano); Cevada (BRS Marciana) e triticale (BRS 148).Os genótipos foram distribuídos em 36 parcelas experimentais, num delineamento experimental inteiramente casualizado, com 12 tratamentos e três repetições. As análises de valor nutritivo e composição mineral foram feitas pelo método da reflectância do infravermelho proximal (NIRS), em amostras do estrato superior a 10 cm de altura da forragem. Os genótipos de aveia e o trigo BRS Umbu apresentaram os melhores resultados de valor nutritivo. A composição mineral apresentou pequena variabilidade entre os genótipos testados. Os resultados demonstram que os cereais de inverno produzem forragem de elevado valor nutritivo.<br>The objective of this research was to evaluate the nutritive value of the forage of 12 genotypes of six double purpose (forage and grains) winter cereal species submitted to harvest in the region of Depressão Central in Rio Grande do Sul state. The species and genotypes tested were: wheat (BRS 277, BRS Guatambu, BRS Tarumã and BRS Umbu); black oat (Agro Zebu, UPFA 21 - Moreninha and Commom black-oat); white-oat (UPF 18); rye (BR 1 and BRS Serrano); barley (BRS Marciana); and triticale (BRS 148). The genotypes were distributed in 36 experimental plots in completely randomized experimental design, with 12 treatments and three replications. Analysis of nutritive value and mineral composition were performed by the near infrared spectroscopy (NIRS) in samples of stratum greater than 10 cm height of forage. Oat genotypes and BRS Umbu wheat presented the best nutritive value results. Mineral composition presented small variability among the genotypes tested. The results demonstrate that winter cereals produce high nutritive value forage