Papers of the week – GABRA1 and STXBP1 in Dravet, gene therapy & synonymous mutations in cancers

FASTA, FASTQ, SAM, BAM, BWA, GC, GATK, IGV. Phew. Day 2 at the EuroEPINOMICS bioinformatics workshop in Leuven. Usually my work starts after the initial NGS raw data quality control and mapping procedures. Today’s topics are supposed to improve my understanding of sequencing analysis and NGS data interpretation. While we are still struggling, other scientists have done their home work already. Here are some of the remarkable publications from this week.

Leuven

Biologists, physicians and computer scientist at the EuroEPINOMICS bioinformatics workshop 2014 in Leuven

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Papers of the week – 15q11 duplications, Olig1 & Automated decision-making

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A productive week in epilepsy genetics.  Scientists and editors were certainly busy this week reporting novel variants and deletions as well the experimental and statistical advances for their interpretation.

A de novo GRIN2A missensmutation in early-onset epileptic encephalopathy. We and others have associated variants affecting the GRIN2A gene with a range of childhood focal epilepsy syndromes. Continue reading

A PhD in genomics – lessons learned

This is it! With finishing my PhD I have become an “adult” member of the scientific Graduierungcommunity. 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

Traveling beyond the ion channel

A how-to guide. July is going to be a slow month for the EuroEPINOMICS blog. Both Roland and I are going on vacation and we will use this time to migrate the entire blog to a more stable and supported server environment. While this always sounds like a quick thing to do, it involves much testing, experimenting and debating and that’s why the Channelopathist will be closed for the month of July. However, we wanted to use this time to provide our readers with brief instructions on how to navigate this blog and our past entries. Speaking of vacation, how far have you traveled beyond the ion channel? Continue reading

Dealing with the genetic incidentaloma – the ACMG recommendations on incidental findings in clinical exome and genome sequencing

Clinical genome sequencing. While exome and genome sequencing is widely used as a research tool, these technologies are also routinely applied in a clinical setting. As with many other data-rich diagnostic tests in medicine, there is an ongoing question on how to deal with potentially relevant findings that turn up indicentally. Now the American College of Medical Genetics and Genomics (ACMG) has released their long-expected recommendations on data return of incidental findings in clinical exome and genome sequencing. Their recommendations provide an interesting basis for discussion on what to do with genetic findings that are found by chance. Continue reading

FS and FS+ are two distinct diseases, as suggested by twins

GEFS+ reloaded. The genetics of Febrile Seizures (FS) is one big mystery. Even though large families have been reported and multiple linkage studies have been performed, no single susceptibility gene for Febrile Seizures is known. This is somehow surprising, given that FS is by far the most common epilepsy syndrome. In contrast to common FS, genetic research has been very successful in families with Genetic Epilepsy with Febrile Seizures Plus (GEFS+), where Febrile Seizures Plus (FS+) are the most striking feature in families.  Ever since the definition of the GEFS+ spectrum was established, the distinction from common FS has been a matter of debate. Now a twin study in Epilepsy Research suggests FS and FS+ might actually be two very distinct diseases with little genetic overlap. Continue reading

The Pareto Principle versus the Long Tail

80/20. In every scientist’s life there is a point when someone points out to you that you should not waste your time and that you should work more efficiently. If that someone, be it your boss, supervisor or close friend with a superior track record, is inclined to resort to management language, you might hear about the Pareto Principle or the Eisenhower matrix. Follow me on a brief motivational blog post that your boss probably doesn’t want you to read – telling you why it is good to keep doing what you are doing. 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

CASK aberrations in Ohtahara syndrome

Suppression-burst. Ohtahara Syndrome is a rare epileptic encephalopathy with onset in the first weeks of life. The typical EEG feature of Ohtahara Syndrome is suppression-burst activity, suggesting a profound disruption of cerebral function. Ohtahara Syndrome can be caused by severe brain malformations and neurometabolic disorders. In addition, mutations in ARX and STXBP1 are known causes of Ohtahara Syndrome. In a recent publication in Epilepsia, genetic alterations in CASK were identified in patients with Ohtahara Syndrome and cerebellar hypoplasia. Given that CASK mutations are the known cause for a complex X-chromosomal disorder, this report provides us with an interesting example of what happens when genes underlying distinct clinical dysmorphology syndromes cross over to the epilepsies. Continue reading

Missed SCN1A mutations in Dravet Syndrome – a matter of degrees

Back from AES. I have just come back from the 66th Annual Meeting of the American Epilepsy Society and I would like to share some of the most recent findings that were presented at this meeting. Since we felt that our presentation on the “re-discovery” of SCN1A mutations in SCN1A-negative patients with Dravet Syndrome received quite some attention, I thought that I would share this part of our presentation as a brief screencast. In particular, I would like to thank Anna-Kaisa Anttonen and Anna-Elina Lehesjoki for providing us with the trace files. And of course thanks to everybody in RES who was involved in this.