Disease-causing genetic mutations that trigger diseases such as cancer have been found in “junk” DNA, it was revealed last night.
Scientists say their new method of investigation identifies variants in the under-explored regions of non-coding DNA that influence activity of other genes and reveals many potential genetic variants that drive the development of a variety of different cancers.
Using the full set of genetic variants from the first phase of the 1000 Genomes Project with information about the non-coding regions generated by the ENCODE Project, the researchers from Wellcome Trust Sanger Institute and Yale University, USA, have already revealed nearly 100 genetic variants implicated in the development of cancers.
Writing in Science, they say they believe their new approach will also help scientists to find other disease-causing variants.
Senior study author Professor Mark Gerstein, from Yale University, said unlike the coding region of the genome, where our 23,000 protein-coding genes lie, the non-coding region – often termed “junk” DNA – is poorly understood, despite making up 98% of our genome.
He said the new information will enable researchers to sieve through the non-coding regions and identify the most functionally important regions.
“Our technique allows scientists to focus in on the most functionally important parts of the non-coding regions of the genome,” he says. “This is not just beneficial for cancer research, but can be extended to other genetic diseases too.”
The discovery comes after the team found that some non-coding DNA regions displayed almost the same low levels of variation as protein-coding genes.
They looked at specific single DNA letters within these so-called ultrasensitive regions of the non-coding DNA regions and discovered that when they are altered, they cause the greatest disturbance to the genetic region and could cause a knock-on effect, resulting in disease.
“Our method is a practical and successful way to screen for purifying selection in non-coding regions of the genome using freely available data such as those from the ENCODE and 1000 Genomes Projects,” says Dr Yali Xue, author from the Wellcome Trust Sanger Institute. “It really shows the value of these large-scale open access data-sets.”
Dr Chris Tyler-Smith, lead author from the Wellcome Trust Sanger Institute, says the method can be applied to find any potential disease-causing variant in the non-coding regions of the genome.
“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,” he adds.
Ekta Khurana, Yao Fu et al. Integrative annotation of variants from 1,092 humans: application to cancer genomics.Science, 3 October 2013.
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