A quarterly publication of the Autism Research Institute

The Autism Research Review International is quarterly publication of the Autism Research Institute

Spring, 2018 | Number 2, Volume 32

Study points to mutations in “junk” DNA as a factor in autism

A new study indicates that some cases of autism spectrum disorder (ASD) may involve mutations in so-called “junk” DNA—that is, parts of the genome that do not encode proteins.

Jian Zhou and colleagues used artificial intelligence techniques to explore the genomes of 1,790 individuals with autism and their unaffected parents and siblings. The families had no history of autism, indicating that the gene defects in the individuals with ASD probably stemmed from spontaneous mutations.

The researchers created a framework that predicted the specific regulatory effects and harmful impacts of gene variants. They used their model to predict the ramifications of non-inherited, noncoding mutations in each child with autism and then compared these predictions with the effects of the same (unmutated) strand in the child’s neurotypical sibling. 

The researchers found that the number of autism cases linked to noncoding mutations was comparable to the number of cases linked to protein-coding mutations that disable gene function. Analysis suggested that noncoding mutations in many of the individuals with ASD altered gene regulation. In addition, it suggested that the mutations affected gene expression in the brain and genes responsible for neuronal development and synaptic transmission.

Study coauthor Olga Troyanskaya comments that the implications of the work extend beyond autism. She says, “This is the first clear demonstration of non-inherited, noncoding mutations causing any complex human disease or disorder.”


“Whole-genome deep-learning analysis identifies contribution of noncoding mutations to autism risk,” Jian Zhou, Christopher Y. Park, Chandra L. Theesfeld, Aaron K. Wong, Yuan Yuan, Claudia Scheckel, John J. Fak, Julien Funk,

Kevin Yao, Yoko Tajima, Alan Packer, Robert B. Darnell, and Olga G. Troyanskaya, Nature Genetics, Vol. 51, May 27, 2019, 973-80. Address: Olga G. Troyanskaya, [email protected].


“New causes of autism found in ‘junk’ DNA,” news release, Simons Foundation, May 27. 2019.