Oxford Events, the new replacement for OxTalks, will launch on 16th March. The two-week OxTalks freeze period starts on Monday 2nd March. During this time, there will be no facility to publish or edit events. The existing OxTalks site will remain available to view during this period. Once Oxford Events launches, you will need a Halo login to submit events. Full details are available on the Staff Gateway.
Large-scale genomic analyses have identified hundreds of genes associated with neurodevelopmental disorders, often via heterozygous de novo mutations. To treat these disorders, we need to clarify whether they act via a loss-of-function or gain-of-function mechanism and how this correlates with phenotype. Looking at the mutations identified, many genes are enriched for protein-truncating variants, in keeping with a loss-of-function/haploinsufficiency model. In contrast, many other genes are enriched for missense variants often at recurrent loci, in keeping with a gain-of-function model. Through phenotype and functional analyses of the genes SCN2A and SLC6A1, an alternative explanation arises: that most variants are loss-of-function and a combination of protein vulnerability and hypermutable loci underlie missense enrichment and recurrence.
