People with autism spectrum disorders have more mutations in their DNA than do their unaffected siblings. The emerging picture is that the genetics of autism is very complex: Dozens or perhaps even hundreds of different mutations may contribute to the disease in each person with autism.

The mutations that predispose a person to developing autism tend to occur in and around genes that are active in the brain as it matures. In particular, many people on the autism spectrum have increased numbers of ‘copy number variations’ (CNVs) — segments of chromosomes that are either absent or duplicated.

These CNVs can result in altered expression levels of specific genes. Although CNVs appear to play an important role in autism, evidence suggests that there must be other types of genetic variation that also contribute to the disorder.

Joseph Corbo and his colleagues at Washington University in St. Louis plan to identify and characterize regions of the genome that may harbor mutations contributing to autism spectrum disorders. Specifically, they hypothesize that regulatory regions of DNA called cis-regulatory elements (CREs), which control the expression of autism-related genes in the cerebral cortex, may represent prime locations for such mutations.

Corbo and his colleagues are in the process of developing a new technology called CRE-seq to evaluate the effects of mutations in CREs throughout the genome. Unlike previous approaches that analyzed CREs one at a time, CRE-seq allows the investigator to study thousands of CREs in a single experiment. Using this approach, it may be possible to discover new autism-related mutations across the entire genome and thereby improve our ability to diagnose, and eventually treat, autism spectrum disorders.