Method Helps Identify Regions in 'Junk' DNA Where Disease-Causing Mutations Occur

A new method enables researchers to identify DNA regions within non-coding DNA where mutations can lead to disease, including cancer.

Despite making up 98 percent of our genome, non-coding DNA is little understood and for a long time was considered "junk." Recent studies, however, have begun to find value in these regions.

The most recent report reveals a variety of potential genetic variants within non-coding DNA that drive the development of various cancers. From the information provided, researchers are granted a starting point to sift through the material to identify the most important parts in terms of function.

"Our technique allows scientists to focus in on the most functionally important parts of the non-coding regions of the genome," Mark Gerstein, senior author from the University of Yale, said in a statement. "This is not just beneficial for cancer research, but can be extended to other genetic diseases too."

The researchers used the genetic variants from the first phase of the 1000 Genome Project and information regarding non-coding regions from the ENCODE project in order to identify those areas that accumulated the least amount of variation.

In doing so, the researchers discovered the same low levels of variation in some non-coding DNA regions as protein-coding genes, which are considered "ultrasensitive" areas.

Within the ultrasensitive regions the scientists examined single DNA letters that cause the greatest disturbance to a given genetic region when altered. According to the press release outlining the study, "If this non-coding, ultrasensitive region is central to a network of many related genes, variation can cause a greater knock-on effect, resulting in disease."

The researchers integrated the new information to create a computer workflow that prioritizes genetic variants in the non-coding regions based on the degree to which they are predicted to cause disease.

By applying FunSeq to 90 cancer genomes, the researchers found nearly 100 potential non-coding variants, though, they note, the system can be used for much more than cancer research.

"Although we see that the first effective use of our tool is for cancer genomes, this method can be applied to find any potential disease-causing variant in the non-coding regions of the genome," says Dr Chris Tyler-Smith, lead author from the Wellcome Trust Sanger Institute. "We are excited about the vast potential of this method to find further disease-causing, and also beneficial variants, in these crucial but unexplored areas of our genome."