Want to learn about epilepsy genetics more effectively? Keep reading…

Demystify. In an earlier post, Ingo blogged about the exciting new Genetic Literacy series that should appear in Epilepsia later in 2014. When we first had the idea at the International Epilepsy Congress in Montreal, we conceived of the Genetic Literacy series as a practical learning resource for practising clinicians and healthcare professionals. We really want to use this opportunity to demystify epilepsy genetics and make this information accessible and useful to readers. Continue reading

Why you need to know what EGI stands for

 

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 genetic architecture toolkit – modeling polygenic disease with rare variants

Architecture. Even though we often write about novel gene findings in the epilepsies, we assume that most epilepsies are complex genetic or polygenic. Polygenic inheritance suggests the genetic architecture is composed of multiple interacting genetic risk factors, each contributing a small proportion to the disease risk. However, when using the phrase genetic architecture, sometimes I am not quite sure what I actually mean by this. For example, how many genes are needed? This is why I wanted to build a model genetic architecture and explore what happens if we build a genetic disease solely from rare risk variants. Follow me to a brief back-of-the-envelope calculation of how this might work.

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How to become a pediatric neurologist

Milestones. Today I passed my board exam for pediatric neurology or neuropediatrics, as we call it in Germany. Even though I am usually not big on celebrating occasions like this, I wanted to use this blog post to reflect upon a journey that led me to three different continents and started eleven years ago in the foothills of AppalachiaContinue reading

“Dark social” or “Who is afraid of email?”

Heathrow. Dark social? Threat? I’ll get back to that. I am writing this wrap-up post for the SpotOn 2013 meeting overlooking the British Airways planes on their way to take-off. In the last two days, we caught a glimpse of what online science communication is about. On Saturday, we had our own session #solo13blogs on using blogs for peer-to-peer science communication. As a science communication newbie, I am happy that our session was well received and stimulated quite some discussion. I have taken away three things from this meeting – a new understanding of our readership, an appreciation for Open Access and data sharing, and finally, a fear of the destructive power of dark social that also applies to epilepsy genetics research. But first things first. Continue reading

An inconvenient truth – segregation of monogenic variants in small families

Climate change. In the era of exome and genome sequencing, it might be worthwhile revisiting the merit of family studies in epilepsy research. Seizure disorders are known to have a highly diverse genetic architecture. When singleton studies identify a single, unique gene finding, this discovery usually does not provide much information about the potential causal role of the variant given the high degree of genomic noise. In contrast, family studies are usually considered more robust, as segregation of variants can be traced. Here is the inconvenient truth: unless the family is very large, segregation of possibly monogenic variants adds little information given the vast amount of variants present in our genomes. Continue reading

The mosaic brain – single neuron copy number variations in humans

Variability. It has been rumored for quite some time, but only now is solid evidence present to show this phenomenon: the high degree of genomic diversity of human neurons. In a recent paper in Science, the genomic diversity among frontal brain neurons is explored on a cell-by-cell basis. The results are breathtaking: up to 40% of frontal cortex neurons have altered genomic material affected by large deletions or duplications. This study provides the linchpin for a plethora of new investigations aiming to understand the impact of this phenomenon in health and disease. Continue reading

Beneath the surface – the role of small inherited CNVs in autism

Grey zone. Structural genomic variants or copy number variations (CNV) can be reliably assessed using array comparative genomic hybridization (array CGH) or Single Nucleotide Polymorphism (SNP) arrays.  However, for deletions or duplications smaller than 50-100 kB, these technologies have a poor detection rate with many false positive and false negative findings unless platforms are used that target specific candidate regions. Exome analysis, on the other hand, is capable of assessing genetic variation reliably on the single base-pair level. Between both technologies, there is a grey zone of structural genomic variants that are difficult to detect; CNVs smaller than 50 kB are often difficult to assess, and the extent and pathogenic role of these small CNVs is unclear. Now, a recent paper in the American Journal of Human Genetics manages to detect small CNVs through exome data. Their analysis in patients with autism, parents, and unaffected siblings suggests a contribution of small inherited CNVs to the overall autism risk. Continue reading

Relationship quality equals bandwidth – a love letter to my wife

Transatlanticism. This is the 165th post on this blog. My wife Katie read every single one of them, correcting my Denglish phrases, adding Oxford commas, and giving me valuable feedback from her unique perspective as a certified genetic counselor with a research background in epilepsy genetics. Today is Katie’s birthday, and I would like to dedicate this post to her by saying thank you and I love you. Katie and I met at the Epilepsy Research Centre in Melbourne, Australia. In 2007, while driving around Lake Alexandrina in South Australia on a road trip, we listened to Transatlanticism by Death Cab for Cutie. This song became emblematic of our relationship for the years to come while we maintained a long-distance relationship between the US (Katie’s Masters in genetic counseling) and Germany (my residency in Kiel). In 2009, after two years of living on different continents, we were finally reunited. If you were to ask me about the main lesson I took away from this time apart, I would sum this up in a single sentence: “Relationship quality equals bandwidth”. This post is a reflection on why quality matters in the communication between geographically separated individuals. It won’t be a purely romantic post. That’s not my style, and that’s ok with Katie – she has corrected this post, as well. Continue reading

Live at Covent Garden – the ERC Starting Grant Interviews

On stage. I just got back from Brussels where I had to defend my ERC Starting Grant in front of the Neuroscience Panel. The European Research Counsil (ERC) Starting Grants are prestigious excellence grants and I was lucky enough to be invited for the famous second round. This second round requires the applicants to go to Brussels in order to give a 10-15 min presentation and defend the application on the 24th floor of the Covent Garden building. It provides a wonderful view of the city, but nobody really bothered taking this in. Let’s use the opportunity to quickly discuss grants, funding and the future of epilepsy genetics. Continue reading