A team of scientists from The Autism Genome Project Consortium have identified significant changes in the DNA of individuals with autism. Composed of over 175 Canadian and international scientists, the Consortium has been conducting an ongoing study of the genes in autistic individuals since 2000, and after 10 years of research into the second phase of their experiment, they have made considerable developments in the understanding and treatment of Autism Spectrum Disorders.
The study is the largest of its kind to address ASDs, and was conducted using 1,500 North American and European families with at least one autistic child, as well as a large group of control individuals who did not possess autism-related genes. It was led by Prof. Stephen Scherer, corresponding author of the study, director of the McLaughlin Centre at U of T, and senior scientist and director of the Centre for Applied Genomics at SickKids, along with Dr. Peter Szatmari, co-principal investigator, director for the Oxford Centre for Child Studies, and professor at McMaster University. Dr. Dalila Pinto, a post-doctoral research fellow at SickKids, was the lead author of the study.
ASDs constitute a group of developmental conditions characterized by communication difficulties and challenges in social interaction and understanding. One in 110 individuals is diagnosed with an ASD, and it is four times more common in males than females. Currently there are no drugs to treat autism, but the developments made by the Autism Genome Project Consortium have made it possible to detect some of the genes involved with autism early on, thereby allowing individuals with ASDs to receive treatment and intervention.
Researchers in the study used the highest possible resolution microarrays — also called gene chips — to scan the genomes of the study participants. The microarrays contain DNA probes (short fragments of DNA used to detect a specific sequence of bases in the target DNA) from across the human genome, and can scan a million different reference points across the gene. Scherer notes that it was a lengthy process that required much time.
By conducting studies on twins with identical genomes, Scherer and his team were able to confirm the finding that autism is genetic. In particular, they confirmed that one particular genetic variation, called a copy number variation is involved in autism. CNVs occur when an individual has one or three copies of a gene, instead of having the regular two copies that are held by the majority of the population.
The researchers found that one subset of individuals with autism had more CNVs than the control group of people without the disorder. In some cases, the genes were inherited, but in others there were new changes that were specific to autistic individuals. These new changes were found in about six percent of the individuals with autism.
Researchers were also able to identify many of the genes connected with autism that were previously unknown before the study was conducted. The study showed that there were CNVs hitting hundreds of genes that are known to be involved in the development of the brain. The researchers then took all the genes affected by CNVs and created a cellular network map. In doing so, they found that the genes affected were involved with proteins that all interact and communicate with one other, and which were all associated with brain development.
These findings are important because knowing many of the genes involved in autism — particularly the four rare genes mentioned in the article by Scherer and his team published in the June 9 edition of Nature Magazine — means that autism can be detected early if an individual is found to possess one of these genes.
In relation to the developments in the treatment and study of autism, researchers have also made progress in the treatment for Fragile X syndrome, an intellectual disability involving 30% of the symptoms associated with autism. In finding the gene that causes Fragile X syndrome, scientists have developed animal models of the gene on which they can test drugs.
Phase 3 of the Autism Genome Project will involve developing drugs to treat the autistic genes, as researchers have already done for Fragile X syndrome. As Scherer stated, “Being able to string together genes and proteins that encode into the same functional pathway gives more possible entryways into the pathways,” thus allowing scientists to have more targets and allowing them to modulate the entryways.
The project has made great leaps in the study and understanding of ASDs. As Scherer stated, concerning the recent developments of the project: “[We can now] really design, in a rational way, therapeutics as opposed to just stabbing in the dark as we were all along.”
