Researchers have identified a molecular map made up of genes previously associated with autism.
Lead study author Prof. Michael Snyder, of the Stanford Center for Genomics and Personalized Medicine at Stanford School of Medicine in California, and colleagues publish their findings in the journal Molecular Systems Biology.
In the US, autism prevalence has increased significantly over the past decade. It is estimated that around 1 in 68 children now have the disorder, an increase from 1 in 125 children in 2004.
Although the exact causes of autism are unclear, researchers are increasingly pointing to genetic mutations as a contributing factor.
In September, Medical News Today reported on a study suggesting mutations in a gene linked to the brain - called TBR1 - may be a cause of autism. And another study, reported by MNT in July, claimed almost 60% of autism risk is genetic and most of the implicated variant genes are common among the general population.
Prof. Snyder notes, however, that the large number of clinical mutations that arise over an array of autism-related human genes makes the disorder difficult to study.
"We, therefore, wanted to see to what extent shared molecular pathways are perturbed by the diverse set of mutations linked to autism in the hope of distilling tractable information that would benefit future studies," he adds.
Corpus callosum brain region, oligodendrocyte cells contribute to autism
To reach their findings, the team used the BioGrid Database of Protein and Genetic Interactions to create an "interactome," which displays all molecular interactions within a cell.
- Autism is almost five times more common among boys than girls
- Parents who have a child with autism have a 2-18% chance of having a second child with a disorder
- Around 46% of children with autism possess an intellectual ability that is above average.
Prof. Snyder says he and his team identified a particular module within the interactome that consists of 119 proteins and shows a "very strong enrichment for autism genes."
To establish a link between the protein interaction module and autism-related genes, the researchers used the Allen Human Brain Atlas to analyze gene expression and conducted genome sequencing on 25 patients.
From this, the team was able to confirm that the protein interaction module is involved in autism. What is more, the autism-related genes found in the module were also identified in a group of 500 patients who underwent exome sequencing.
Using genome sequencing, RNA sequencing, antibody staining and functional genomic evidence, the team also found that a brain region called the corpus callosum and brain cells called oligodendrocytes play a role in autism.
"The module we identified which is enriched in autism genes had two distinct components," explains Prof. Snyder. "One of these components was expressed throughout different regions of the brain. The second component had enhanced molecular expression in the corpus callosum. Both components of the network interacted extensively with each other."
The researchers suggest that interference in parts of the corpus callosum disrupts the signaling between the two halves of the brain, which is likely to cause the characteristics of autism.
Commenting on their findings, Prof. Snyder says:
"Our study highlights the importance of building integrative models to study complex human diseases.
The use of biological networks allowed us to superimpose clinical mutations for autism onto specific disease-related pathways. This helps finding the needles in the haystack worthy of further investigation and provides a framework to uncover functional models for other diseases."
Earlier this month, MNT reported on a study published in the journal Environmental Health Perspectives, which suggested that women exposed to high levels of fine particulate matter during pregnancy may be at much higher risk of having a child with autism.