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

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

Transporte de oócitos bovinos em meio de maturação por diferentes períodos de tempo sem controle da atmosfera gasosa

Avaliou-se a viabilidade do transporte de oócitos em meio quimicamente definido, e analisou-se a necessidade da adição ou não de hormônios neste meio. Os oócitos do grupo-controle (0h) foram maturados por 24h em estufa de CO2, e os dos grupos experimentais foram transportados em incubadora portátil. No experimento I, as taxas de clivagem foram similares (P>0,05) para os grupos 0h (59,7%), 3h (53,5%) e 9h (48,8%), e houve redução nos grupos 6h (46,1%) e 12h (43,8%). Essas taxas foram semelhantes entre os grupos 3h, 6h, 9h e 12h. A produção de blastocistos não foi diferente (P>0,05) para os grupos 0h (38,0%), 3h (32,3%), 6h (27,3%) e 9h (24,8%), e houve redução no grupo 12h (18,9%). Essas taxas foram semelhantes entre os grupos 6h, 9h e 12h. No experimento II, não houve diferença (P>0,05) entre as taxas de clivagem para os grupos 0h (71,4%), 3h (70,3%), 6h (56,0%) com hormônios, e os grupos 3h (64,8%) e 6h (54,1%) sem hormônios. A produção de blastocistos foi similar (P>0,05) para os grupos 0h (46,1%), 3h com hormônios (45,8%) e 3h sem hormônios (41,1%), porém houve redução nos grupos 6h com hormônios (35,5%) e 6h sem hormônios (33,5%). Essas taxas foram semelhantes entre os grupos 3h sem hormônios e 6h com e sem hormônios. Estes resultados indicam que é possível otransporte de oócitos bovinos por um período de até nove horas, e que a adição de hormônios neste meio não influencia os índices de clivagem e de blastocisto