At least 100 different genes have been implicated in autism spectrum disorders. Although certain genetic variations do correlate with autism, other factors must be involved, as not all individuals with these genetic variations develop an autism spectrum disorder.

Louis Kunkel and his colleagues at Boston Children’s Hospital investigate epigenetic mechanisms, which change gene expression without altering the underlying DNA sequence. Their theory is that epigenetic mechanisms could increase the likelihood that certain genetic variants will lead to autism. They used peripheral blood gene expression profiles from a variety of autism subtypes to begin developing a molecular diagnostic test, which is currently in clinical development.

With collaborators at Emory University in Atlanta, Kunkel carried out microarray-based profiling of both RNA expression and DNA methylation, a type of epigenetic change, in 46 sibling pairs in which one sibling has autism and the other does not. The researchers found 118 differentially expressed genes and 621 loci with significantly changed DNA methylation profiles.

Differential splicing patterns highlight pathways and gene-environment mechanisms that may play a role in autism. The researchers identified hundreds of novel splice isoforms, and 59 of these were found exclusively in people with autism. These 59 isoforms belong to 55 genes, many of which are part of the toll-like receptor signaling pathway.

Finally, using postmortem brains from individuals with autism, Kunkel’s group found altered RNA editing of synaptic genes, suggesting that RNA editing could be an epigenetic mechanism that plays a role in autism.