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

Pedagogical and political encounters in linguistically and culturally diverse primary classrooms: examples from Quebec, Canada, and Gauteng, South Africa

Comparative research in multilingual urban primary schools indicates that the pedagogical and political goals of schooling may operate at cross-purposes. Classroom observations and teacher interview-discussions were conducted in classes for immigrant children in Montreal, Quebec, Canada, where the language of instruction is French, and in classes in Pretoria, Gauteng Province, South Africa, where children from many different language backgrounds are taught in English. Two main themes emerged: (1) Pedagogically, effective teacher-learner communication can break down when teachers are unaware of the roles that language and culture play in second language classrooms. (2) Politically, efforts to assimilate learners into new socio-cultural/political contexts sometimes take precedence over sound pedagogical practice, such as drawing on the linguistic and cultural repertoire that learners bring to the classroom. This on-going qualitative research underlines the importance of preparing pre-service and inservice teachers for the linguistic and cultural diversity they are bound to encounter in their classrooms, and of deepening their understanding of the influence of such diversity on the teaching-learning process.http://www.tandfonline.com/loi/ccom20gv201