Role of ETS2 in autoimmune and inflammatory diseases

Interviewer: Dr. James Lee from The Francis Crick Institute, thank you very much for your time today. Your recent publication in Nature demonstrates how functional genomics can turn genetic findings into useful insights by identifying disease causes and therapeutic opportunities. To start, can you provide a brief summary of the research? What was the challenge you identified, and the approach that you took to meet it? Dr. Lee: Of course, thanks very much for the invitation to join you today. We were interested in a genetic association that, interestingly, we've known about for about ten years. The same set of genetic variance on chromosome 21 has been linked to the development of at least five different inflammatory diseases, but nobody really knows what on earth is going on at this site, because the site of the association, the region where all the interesting thing is happening, actually turns out to be what we call a gene desert. It's a region of our DNA that doesn't contain any genes whatsoever. We were interested in that, because we thought, well, first of all, it must be fundamentally important if it's increasing your risk of four or five different diseases. Secondly, we had an idea that it might contain what we call an enhancer. Now, enhancers are a bit like the volume dials in your genome. They turn up or turn down the amount of nearby genes, and they can sometimes need quite a bit of space. We figured that maybe there's a really big enhancer in this region that's important in controlling a gene that might be doing something fundamentally important, so we started off going looking for that. Actually, what we ended up finding was,