Decoding the "Dark Matter" Within
On September 5th, scientists published the results of a multi-year, international study attempting to answer these questions. This project, dubbed ENCODE for Encyclopedia of DNA Coding Elements, made great strides towards dissecting the role of this non-coding DNA. Twelve years ago, scientists were surprised to find that so little of the genome actually codes for proteins; this time around, scientist were surprised to find that so much of the non-coding region seems active in some way. As much as 80% of this DNA now appears to be in play, either in regulating the use of the protein coding regions, or in producing RNA molecules which do not directly make proteins but play some other role – in some cases, an as yet to be determined role.
This finding has direct implications for drug discovery research. Over the past decade, scientists have identified a number of small changes in the genome sequence – dubbed single nucleotide polymorphisms (SNPS) – between people who suffer from certain diseases such as Crohn’s disease, asthma, rheumatoid arthritis, type 1 diabetes, type 2 diabetes, bipolar disorder, and coronary artery disease, amongst others. Certainly some of these differences were identified in genes; however, many also exist in the non-coding regions. This opens up a whole new arena for drug discovery – the possibility of targeting not just the disease protein itself, but also how it is regulated. This may prove to be an invaluable approach in those cases where the disease protein is not amenable to therapeutic intervention.
There is still much to be learned. How do the regulatory regions interact with each other? How many different genes does each regulate? And what are all of those RNA molecules doing? Answering even some of these questions will revolutionize our understanding of human genomics and human disease.