Groundbreaking screening tool is the first to map 'junk DNA' for mystery gene mutations that cause cancer, diabetes, and dementia - and experts say it could 'revolutionize medicine'

A new screening tool that maps 'junk DNA' for mutations that cause cancer, diabetes and dementia could revolutionize medicine, experts claim. 

The tool, developed by Columbia University, explores the 98 percent of the human genome often referred to as biological 'dark matter' - because it's as mysterious as space. 

For years, we have written off this unknown mass of DNA as 'junk'.

However, researchers warn it could hold the key to identifying how genes, and genetic reactions to the environment, can cause genetically inherited heart disease, diabetes, cancer and neurological disorders.

The breakthrough could lead to new treatments and even cures for such diseases, which kill millions of people each year. 

In fact, lead investigator Professor David Goldstein claims many scientists and universities are already interested in getting hold of the technology.

We anticipate researchers will immediately start using Orion to help them find pathogenic mutations in patients in which previous sequencing efforts were negative,' said Goldstein, director of the Institute for Genomic Medicine at Columbia.

Currently, identifying single mutations that cause rare, devastating diseases like muscular dystrophy is relatively straightforward.

However, nobody has made much progress in providing a clear explanation for how the human genome triggers illnesses that run in families like cancer and dementia.

Researchers believe the key may lie within this mass of 'dark matter' - i.e.: non-coding DNA.

Despite many successes in DNA research, the impact has been limited on a practical level.

Current sequencing technologies can only identify disease-causing mutations in fewer than a third of patients suspected of having a genetic condition.

A key reason why most investigations turn up empty-handed is the 'dark genome', Goldstein explains.

Although we know the non-coding genome regulates genes, the details remain obscure. As a result, Professor Goldstein says, sequencing data from the entire genome 'is currently considered almost uninterpretable'.

To avoid a pointless pursuit, most scientists who research disease-causing mutations restrict their search to protein-coding genes - which make up only a sliver of the genome.


Orion locates pathogenic mutations in non-coding genes.

It does this by flagging up regions likely to contain disease-causing genetic changes based on their prevalence.

Orion was developed by comparing the entire genomes of 1,662 people with one another and pinpointing stretches of DNA that vary little from person to person.
These regions are 'intolerant' to change so they are most likely doing something important, explained Professor Goldstein.

A mutation in an intolerant region is more likely to cause disease than one in a tolerant - or less important - place.

This prediction was confirmed when the researchers mapped the locations of previously identified non-coding mutations.

The study published in PLOS ONE found more fell within Orion's intolerant regions


Over 90 percent of the genetic variation in the human population that is associated with common disease falls outside of those genes.

There are potentially millions of sites with unknown functions. 

Previous methods to explore the non-coding genome focused on areas that have been retained in multiple species over evolutionary time.

Although this suggests they also have an important function the approach is unable to identify regions that have taken on important new functions in humans.

Professor Goldstein said Orion isn't yet a finished product because as more genomes are sequenced the resolution of regions will improve dramatically.

He said: 'At that point we are optimistic Orion will constitute one helpful tool in the effort to identify variants throughout the genome that influence the risk of both rare and common diseases.' 

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