The post I didn’t write. Last Thursday was Thanksgiving and my daughter’s second birthday. Therefore, even though I initially had grandiose plans for a Thanksgiving post, I did what a family father would do on days like this – not write blog posts. Therefore, having digested the Thanksgiving dinner and having survived Black Friday, here comes our belated Thanksgiving post. Let’s think for a second how we handle the combination of family and research. Continue reading
Category Archives: Ideas
The Biobank Dilemma
Killing two birds with one stone. I am currently preparing for a presentation for the Scientific Advisory Board of our local biobank network P2N and I thought that I wanted to share a few thoughts on biobanking and sample collection for epilepsy genetics that have troubled me for a while. Continue reading
Validation of rare variants – the power of finding anything at all
How much? Last week, we discussed the probability of finding de novo variants in patients with epileptic encephalopathies, but our calculations were only half the story. Genes that are identified through genome-wide sequencing technologies are often validated in additional cohorts. In many cases, we will only be able to establish a given gene as causative if we find another patient with a mutation in this gene. I was therefore asked to write an additional post on power calculations for rare variants in validation cohorts. Let me tell you the story how I stumbled across a little bit of almost forgotten high school math. Continue reading
The Hippocampus Conspiracy
Slightly misleading. The green and blue histological staining that has become the EuroEPINOMICS logo features a human hippocampus, a part of the human brain that is particularly important in human epilepsy. Temporal Lobe Epilepsy (TLE) is the most common epilepsy in adults and involves the hippocampal region. Ironically, TLE is the human epilepsy that has always been at odds with genetic research. Let’s review what we know about the genetics of TLE and “hippocampal genetics”. Continue reading
Jumping genes in the brain – single neuron sequencing of L1 retrotransposons
The not so static genome. We usually think that our genome is static and that differences between cell types usually arise through mechanisms that do not necessarily involve alterations of the DNA structure. This suggestion has been challenged by initial data suggesting that retrotransposons may be particulary active in neurones. Now, a recent study in Cell investigates the role of jumping genes using single-cell sequencing of neurons.
Genome meets Connectome: gene networks and brain microstructure
Genetic imaging. There are two major fields in epilepsy research – functional imaging and genetics. Both fields live parallel lives and hardly ever interact. When they do, the interaction is usually short-lived and full of disappointments, as nothing has really ever worked. However, a grant application due today has led me to a recent publication in the Journal of Neuroscience, which combines imaging and GWAS. And believe it or not, the ion channels are back. Continue reading
Close encounters of the third kind – rare genetic variants in families
A new beast. Rare genetic variants probably account for a significant fraction of the genetic liability to many common and rare disorders. Rare variants occupy the liability space between monogenic variants and common genetic variants. Their existence has often been postulated, and genetic investigations looking at copy number variants have elucidated some examples of rare variants. These rare variants appear to carry particular properties that are quite unexpected including the way that these variants run in families. Now, in a recent paper in the European Journal of Human Genetics, we have developed a model of the way rare variants behave in families. And there is a lot of misbehaving. Continue reading
The London 2012 ECE in retrospect
The Shard. London has changed quite a bit since my last visit and I didn’t really pay that much attention to the Olympics, I must admit. Both became clear to me when I left the train at London Bridge Station. There it stood in front of me: The Shard. London’s new high-rise building, the tallest skyscraper in the European Union. And I had no idea that it even existed. On a smaller scale, there were also a few surprises for me at the ECE in the world of epilepsy genetics. Continue reading
Rolandic Epilepsy Explained?
Soundbites. I am very happy to have been part of the 1st Waterloo Foundation Meeting on the Idiopathic Focal Epilepsies of Childhood, which took place at King’s College in London on September 29th, 2012. This meeting was exclusively dedicated to everything rolandic. While the 10th European Epilepsy Congress is just getting started, we thought that we could provide you with a few soundbites from this meeting. And — by the way — rolandic epilepsy is far from being explained. Continue reading
The years of our fathers: paternal age and the rate of de novo mutations
Aging fathers. An increase in risk of aneuploidies, i.e. chromosomal aberrations such as Trisomy 21, is well established with maternal age. Whether the paternal age also increases the risk for disorders in the offspring had long been disputed. However, a connection between paternal age and autism has been found in recent years. Now a recent study in Nature finds a surprisingly strong correlation on the genetic level… Continue reading
