SHANK3, epilepsy, and the excitatory/inhibitory imbalance

Postsynaptic. SHANK proteins are elements of the postsynaptic density, linking synaptic transmission with the cytoskeleton. Deletions in SHANK2 and SHANK3 are known genetic risk factors for a broad range of neurodevelopmental disorders. The role of the reciprocal duplications, however, has remained unclear. In recent paper in Nature, a novel mouse model expressing a SHANK3 transgene is investigated. The results of a mere 1.5 fold overexpression of the protein are dramatic, hinting at unanticipated mechanisms that regulate the balance between excitation and inhibition.  Continue reading

This week on the ‘omics blogs

New format. We have mentioned earlier that we wanted to try a few new formats on this blog including providing you with a summary of what happened on the web this week in neurogenetics. Plus a little update on what we are working on currently.

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Hypermutability of autism genes: lessons from genome sequencing

Pushing past the exome. Family exome sequencing has become a standard technology to identify de novo mutations in neurodevelopmental disorders including autism, schizophrenia, intellectual disability and epilepsy. Despite the many advances in the field, exome data is confusing and difficult to interpret. Accordingly, we were wondering what the increase from exome sequencing to genome sequencing might add other than more data and more questions. Now, a recent paper in Cell reports on family-based whole-genome sequencing in autism. And some of the results are quite surprising. Continue reading