This is what you will see in epilepsy genetics in the next five years

Welcome to our new blog. We have moved our blog to a new server, and this is the first post on our new platform. Let’s start out this new era with a general overview of what will happen in the field of epilepsy genetics in the next five years. We definitely plan to follow the developments as we did over the last two years. Here are the six things that we will look back upon in five years.

Why we moved. As we explained on our final post on the old Channelopathist blog, it’s about the potential to develop. We would like to expand our blog to be the companion of the emerging Epilepsiome database and need a bit more flexibility than the old platform would have allowed for. There might be temporary setbacks and problems, but that’s part of blogging – things develop in real time.

All we need. Belval Hauts-Fourneaux is reviving itself with biotechnology and art. I the context of the data analysis meeting this question is quite provocative. Do we have all we need?

All we need. Belval Hauts-Fourneaux in Luxembourg is reviving itself with biotechnology and art. As I am currently struggling to upload new pictures on our blog due to the move (minor hiccup), I am recycling this picture from a previous post. Only two years ago, 1000 exomes seemed unreachable….

The future. Here are the developments that we anticipate in the next five years.

1 – Personalized Medicine
We cannot promise that genetic findings will have a major impact on treatment decisions in the future, but we (the entire epilepsy genetics community) will do our best to find ways to use genetic data for better treatment. Be it large-scale compound screening for components that ameliorate seizures in specific genetic epilepsies, pharmacogenomics, or even clinical trials – we will see these patient-centered studies in the near future. The aim of these studies will be to make our treatment decisions be informed by genetic information.

2 – Big, big data
10,000 thousand, maybe even 50,000 exomes and/or genomes of individuals with epilepsies will be available for data mining, providing the basis for gene discovery at a yet unanticipated level. How do we identify a causative genetic alteration that is present in 1:10,000 patients? By looking at big data.

3 – Moving past the coding regions
I don’t know how yet, but there will be well-powered, sufficiently robust approaches to mine for causative or contributory genetic risk factors outside of exons. It would be very unlikely if these risk factors didn’t exist, but we simply don’t have the approaches to identify them yet in a meaningful way. Watch out for causative mutations occurring in gene deserts, followed by our struggle to understand how they cause epilepsy.

4 – Shift to patient organizations and industry
We already alluded to this in an earlier post. National and super-national funding agencies will slowly pull out of the field of gene discovery. Patient organizations and industry might become major sources for discovering genes and refining the knowledge about known genes. Data generated by the genetic diagnostic industry already outnumbers the massive parallel sequencing data generated on a research basis, and this trend will continue. Ultimately, this is going to be a very positive development, as it broadens the support base for genetic research in the epilepsies.

5 – Predictions
Last week, the genetics blog posted a slightly misleading commentary called “Predicting Autism” that discussed a Nature Genetics paper by Uddim and collaborators. The Nature Genetics publication evaluated novel ways to prioritize de novo mutations in autism based on expression in brain and purifying selection. Even though the results sound very promising, these strategies are helpful in diagnosis, not prediction. Understandably, there is a great need to develop novel screening strategies for neurodevelopmental disorders including intellectual disability, autism, schizophrenia, and epilepsy. The next five years will likely show us the limitations of genetic findings in these disorders when it comes to prediction, shifting the focus to other early-screening strategies.

6 – Surprises
There will be surprises, that’s for sure. Looking back at the last few years, KCNT1 and DEPDC5 came as a surprise. The discovery of KCNT1, the gene for a significant subset of cases with Malignant Migrating Partial Seizures of Infancy, came very unexpectedly to me. Even though the phenotype is well defined, there was no way to predict that this condition is also genetically homogeneous – other well-defined epilepsy phenotypes are not! DEPDC5 emerged as a relatively common gene for familial focal epilepsies, a genetic cause that many people including myself didn’t see coming. We would predict 3-5 additional big surprises in the next five year – of course not knowing what they will be in June 2014.

This post was written by Ingo Helbig and Dan Lowenstein.

Ingo Helbig

Child Neurology Fellow and epilepsy genetics researcher at the Children’s Hospital of Philadelphia (CHOP), USA and Department of Neuropediatrics, Kiel, Germany

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