We have a new paper out today in Science Translational Medicine that describes our application of the massive Exome Aggregation Consortium database to understanding the variation in one specific gene: the PRNP gene, which encodes the prion protein.

This project was a special one for a number of reasons. Firstly, there’s an incredibly strong personal motivation behind this work, which you can read much more about in a blog post by lead author Eric Minikel. Secondly, it’s a clear demonstration of the way in which we can use large-scale reference databases to interpret genetic variation, including flagging some variants as non-causal or having mild effects. Thirdly, as discussed in the accompanying perspective by Robert Green and colleagues, this work is already having clinical impact by changing the diagnosis for people with families affected by prion disease. And finally, the discovery of “knockout” variants in PRNP in healthy individuals is tantalizing evidence that inhibiting this gene in mutation carriers is likely to be a safe therapeutic approach.

The paper is of course open access, so you can read the details yourself. Huge congratulations to Eric for pulling this paper together!