Pushing the button for the next exome sequencing round

Galvanize. Last week, the EuroEPINOMICS RES working groups made the final decisions for the selection of trios for exome sequencing at the Sanger Centre, funded jointly by the Sanger Programme on paroxysmal neurological disorders and the EuroEpinomics RES fund. We pushed the button for 102 patient-parent trios to be sequenced. And for some reason, I caught myself humming “Galvanize“, the 2005 big beat hymn by the Chemical Brothers. 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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The tale of two planets: the expanding spectrum of STXBP1

Intergalactic, planetary. At the end of last year, I gave a presentation on epilepsy genetics for epilepsy surgeons. Having worked in presurgical epilepsy monitoring myself for some time, I could not help realizing that the fields of epilepsy surgery and epilepsy genetics are quite distinct. Both fields use different terminologies and different concepts and virtually represent parallel worlds. In the vast majority of cases, this does not really matter as there is little overlap between the patients undergoing epilepsy monitoring for later surgery and patients where a genetic etiology is assumed. In a recent paper in Epilepsia, the case of a patient with an STXBP1 mutation is presented who successfully underwent epilepsy surgery. So who is right when both fields collide while treating a single patient? Continue reading

Rare variants and olive trees

Epic dimensions. 5,000 years ago, human civilization was getting off the ground in Mesopotamia. At some point, the early human pioneers decided to use pictures as letters and human writing was invented. Ox became aleph, which became alpha, which turned into literature, which finally turned into blogging. At around the same time that the Mesopotamian people invented the direct precursor of modern day tweets and text messages, rare genetic variants started spreading through the human population. In fact, all the rare variation that we see in humans today, had probably not been present prior to the chiseling of the first human words. Continue reading

Gephyrin, the inhibitory synapse and pathogenic microdeletions

GABA, postsynaptic. The molecular structure of the postsynapse has long been a mystery. Why do receptors cluster at a particular site and don’t simply float around all over the plasma membrane? The identification of postsynaptic scaffolding proteins answered some of these questions. However, it also became clear that inhibitory synapses are completely different from excitatory synapses. Now, a recent paper in Human Molecular Genetics finds that exonic deletions in gephyrin, the main structural protein of the inhibitory synapse, predispose to various neurodevelopmental disorders. Continue reading

AUTS2, regulatory elements and human evolution

Recurrent themes. The era of large-scale genomics in neurodevelopmental disorders has welcomed the discovery of several genes, which predispose to a wide range of neurodevelopmental disorders. While a connection to neuronal function is obvious for a few of them, the function of other genes remains cryptic. Now, a recent paper in PLOS Genetics investigates AUTS2, a gene that is both a candidate gene for autism and a gene that has changed dramatically in recent human evolution. Continue reading