Mutations in so-called “junk” DNA have been tied to the development of autism (ASD) in children who do not have parents or siblings with the condition.
The research, published in the journal Nature Genetics, provides an important piece of information in the quest to understand ASD, but also has wider significance.
“This is the first clear demonstration of non-inherited, non-coding mutations causing any complex human disease or disorder,” says lead researcher Olga Troyanskaya of the US Flatiron Institute’s Centre for Computational Biology.
Less than 2% of human DNA codes for the proteins that enable the critical functions of metabolism. The remaining 98% used to be thought of as effectively ballast, characterised as makeweight “junk”.
Today, the label is recognised as a misnomer, and has been largely replaced by the term “non-coding”. Research has shown that at least some of it plays very important roles in regulating the activity of genes – switching them on and off, and variously enhancing or dampening protein-coding activity.
Previous studies have tied about 30% of autism cases in families with no prior history of the condition – so-called “simplex” cases – to mutations in particular coding genes.
Using a machine-learning approach, Troyanskaya and colleagues analysed the genomes of 1790 people, comprising simplex autism cases and their families. Their model was trained to predict how any given DNA sequence would affect gene expression.
The analysis revealed that cases linked to mutations in non-coding DNA should be of the same magnitude as those tied to coding DNA changes.
The approach enables the identification of particular targets within the non-coding DNA which can now be the subject of more intense and focussed research.
A computational biologic approach to DNA function, the researchers say, opens up a broad range of possible avenues for the understanding of conditions driven by genetic function.