Clustered Coding Variants in the Glutamate Receptor Complexes of Individuals with Schizophrenia and Bipolar Disorder

Current models of schizophrenia and bipolar disorder implicate multiple genes, however their biological relationships remain elusive. To test the genetic role of glutamate receptors and their interacting scaffold proteins, the exons of ten glutamatergic ‘hub’ genes in 1304 individuals were re-sequenced in case and control samples. No significant difference in the overall number of non-synonymous single nucleotide polymorphisms (nsSNPs) was observed between cases and controls. However, cluster analysis of nsSNPs identified two exons encoding the cysteine-rich domain and first transmembrane helix of GRM1 as a risk locus with five mutations highly enriched within these domains. A new splice variant lacking the transmembrane GPCR domain of GRM1 was discovered in the human brain and the GRM1 mutation cluster could perturb the regulation of this variant. The predicted effect on individuals harbouring multiple mutations distributed in their ten hub genes was also examined. Diseased individuals possessed an increased load of deleteriousness from multiple concurrent rare and common coding variants. Together, these data suggest a disease model in which the interplay of compound genetic coding variants, distributed among glutamate receptors and their interacting proteins, contribute to the pathogenesis of schizophrenia and bipolar disorders

COMMON SENSE: Cost-effective sensors, interoperable with international existing ocean observing systems, to meet EU policies requirements

COMMON SENSE is a new project that supports the implementation of European Union marine policies such as the Marine Strategy Framework Directive (MSFD) and the Common Fisheries Policy (CFP). The project, which was launched in November 2013, is funded by the EC Seventh Framework Programme (FP7) and has been designed to directly respond to requests for integrated and effective data acquisition systems by developing innovative sensors that will contribute to our understanding of how the marine environment functions. COMMON SENSE is coordinated by the Leitat Technological Centre, Spain, and its consortium brings together 15 partners from seven different countries, encompassing a wide range of technical expertise and know-how in the marine monitoring area