E2 consortium. Infantile Spasms and Lennox-Gastaut Syndrome are two epilepsy syndromes with a strong genetic component. De novo mutations play an important role in genetic epilepsies. However, given the overall mutational noise in the human genome, telling causative genes from innocent bystanders is difficult. In the largest and most comprehensive analysis so far, our E2 consortium just published a joint analysis of 356 patient-parent trios, which were analyzed by exome sequencing. In addition to implicating DNM1, GABBR2, FASN, and RYR3, this publication sends a clear message: the age of gene discovery in epilepsy is over – from now on, genes will find themselves. Let me tell you what I mean by this. Continue reading
Category Archives: Consortia
How to find recessive disease genes for epileptic encephalopathies
The E2 story continues. There has been major progress in identifying the role of de novo mutations in infantile spasms and other epileptic encephalopathies. Over the last two years, more than 20 new genes for epileptic encephalopathies were discovered and we have good evidence suggesting that de novo mutations play a major role in these disorders. Moreover, we have gotten a good sense on how complicated it can be to call a de novo mutation pathogenic given the flood of rare genetic variants in the human genome. However, de novo mutations are not what we think about clinically when assessing a patient with new-onset epileptic encephalopathy. In a clinical setting, we are often concerned about underlying metabolic disorders, many of which are recessive. Accordingly, we felt that the next task of the E2 consortium was to assess the role of inherited variants in epileptic encephalopathies. Just to tell you in advance, it is not as easy as it sounds.
Why you need to know what EGI stands for
Epilepsy Genetics Initiative – A Signature Program of CURE from CUREepilepsy on Vimeo.
The Epilepsy Genetics Initiative. If you had told me last week that the next era of epilepsy genetics would be announced by an animated cartoon, I wouldn’t have believed you. Earlier this week, the Epilepsy Genetics Initiative (EGI) was launched, an emerging large exome repository that will help us connect dots in epilepsy genetics research by centralizing genetic data for research. These are the three things that I have learned from the EGI launch. Continue reading
The final EuroEPINOMICS General Assembly – Impressions from Helsinki
Time flies by. Last week, we have had the final General Assembly of the EuroEPINOMICS project in Tuusula, Finland. All four projects of the EuroEPINOMICS consortium presented the current, ongoing projects and it’s good to hear that there are multiple publications in various stages coming up. Over the three years of the consortium, the diverse groups grew closer together. During this meeting many unpublished results were shown, including extension of studies on genes such as HCN1, CHD2, GRIN2A, GRIN2B or RBFOX1 as well as more data on epigenetics in acquired epilepsy.
The age of mega-genomics, type 2 diabetes, and protective variants in SLC30A8
Sequence first. There are larger genetic studies but not too many. In a recent study in Nature Genetics, roughly 150,000 individuals were genotyped to assess the importance of rare, disruptive variants in SLC30A8 in type 2 diabetes. This genomic tour de force was made possible by available and curated databases that could be tapped to extract the necessary genetic information. Also, this study highlights some of the surprises that we can expect by mining the human genome for disease-related information. Rare, disruptive variants in SLC30A8 protect against type 2 diabetes. Let’s review why these rare, protective genetic factors might be particularly important for biomedical research and what kind of studies we need to identify them. Continue reading
A PhD in genomics – lessons learned
This is it! With finishing my PhD I have become an “adult” member of the scientific 
community. I grew out of a bachelor in biochemistry on transfection methods in neuronal cell lines, a research semester in Canberra with focus on B-cell immunology and master into a PhD in epilepsy genomics. I was involved in the EPICURE IGE copy number projects and recently my work changed to the analysis of rare variants in RE and IGE in the EUROepinomics framework. During this time I was involved in the identification of variants in RBFOX genes and GRIN2A as well as other risk factors which are currently in review. I share my experience and thoughts and hope they help others who are about to or have just started their thesis. The aspects reflect my personal view and some are specific for graduation in disease genomics. Continue reading