The search for the genetic underpinnings of autism spectrum disorder has just yielded a new set of clues. In the largest study to date, the Autism Genome Project consortium reports that people with autism have more copy number variants – segments of DNA that have been either duplicated or deleted – in their genes.
The results, published today in Nature, could eventually be used to develop quick diagnostic tests. The consortium was also able to group some of the affected genes into biochemical pathways. These pathways – some of which are clearly linked to brain function — may then become attractive targets for those who hope to develop drugs to treat the condition.
Autism is a complex disorder. Although the environment is thought to influence the risk of autism, genetics are known to play an important role.
The study included 996 people with autism and another 1,287 people without the disorder, to serve as controls. The researchers focused on rare genetic variants – a shift from previous approaches, which analyzed variants that are commonly seen in the population. (For more on rare variants, see ‘Hunt for genetic causes of diseases causes narrows targets’.)
They found that autistic people did not have more rare copy-number variants than those without the disorder, but their variants were more often found within genes rather than in the vast amount of DNA located between genes. Specifically, 20% more genes contained a rare copy-number variant in autistic participants in the study. And among genes previously linked to autism spectrum disorder or intellectual disability, 70% more of them contained a rare copy number variant.
Deletions in one region of the X-chromosome, called the DDX53-PTCHD1 locus, were associated with a three-fold higher risk of autism spectrum disorder.
Diagnostic tests based on the work will not be clearcut. Co-author Stephen Scherer of the Hospital for Sick Children in Toronto estimated that genetic clues to the disorder were present in only about ten percent of the families with an autistic member in the Canadian cohort of the study. And, the researchers noted, each patient carried their own unique assortment of copy number variations. Of nearly a thousand variants studied, the most prevalent was still only present in less than 1% of the participants with autism.
But a new test would nevertheless be welcome. At present, diagnosing autism can take months or longer – an agonizing wait for anxious parents that can delay the start of behavioural therapies. Early therapy has been shown in some cases to lessen the effects of the disorder.
Meanwhile, the hunt continues. The consortium has enrolled another 1,500 families, and hopes to use next-generation sequencing to sequence full genomes and exomes (the part of the genome that codes for RNA or protein).
Image: Ingram Publishing