Copy number variations (CNVs), or altered numbers of certain stretches of DNA, have been implicated as a genetic cause of autism. Alea Mills and her colleagues at Cold Spring Harbor Laboratory in New York set out to determine whether CNVs in the chromosomal region 16p11.2 cause autism-like phenotypes. They used chromosome engineering to generate mice with a deletion corresponding to 16p11.2 — one of the most prevalent genomic lesions associated with autism — as well as mice with reciprocal duplication of this region.

One copy of 22q11.2, a segment of chromosome 22 that includes several genes, is missing in 1 of every 4,000 individuals. This non-inherited genetic abnormality results in some physical abnormalities, most of which can be repaired surgically early in life. But the most pernicious deficits associated with this microdeletion are cognitive, including severe learning disabilities and a high risk for mental illness, such as autism and schizophrenia. An improved understanding of the mechanisms that contribute to these psychiatric and cognitive symptoms is essential for providing better treatments.

About 15 to 30 percent of children with autism are at risk of epilepsy, which is roughly ten times higher than the general population. Additionally, a significant proportion of individuals with autism who don’t have clinically evident seizures show abnormalities in electroencephalography — a measure of electrical activity in the brain. Some genes implicated in epilepsy, such as the contactin gene family, are also risk factors for autism. And finally, preliminary data suggest that anticonvulsant drugs may be useful for treating some autism spectrum features.

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.

Christopher Walsh and his colleagues at Boston Children’s Hospital have been studying the genetics of autism by analyzing inherited recessive mutations in consanguineous families — those in which the parents are related to each other (e.g., as cousins).

A major goal of autism research is to identify the underlying genetic variants that contribute to risk of the disorder. Knowledge of these genetic variants may yield insight into how and why autism symptoms develop, and ultimately provide a list of potential therapeutic targets.

Four times as many males as females are afflicted with autism. Although there is much speculation about this sex bias, there have not been many well-powered studies designed to identify female genetic susceptibilities and differentiate them from male risk factors. Lauren Weiss and her colleagues at the University of California, San Francisco, set out to map the difference between male and female autism at the level of DNA. Understanding sexual dimorphism at this level may suggest ways to reduce autism risk for males and females.

People with autism spectrum disorders often lack self-awareness, making it difficult for them to interact and empathize with others. Using new genomics methods to study the neurons that are active during self-awareness and empathy, John Allman and Barbara Wold of the California Institute of Technology are learning how these processes are different in people with autism.

Studies focusing on specific genes have made limited progress in unraveling the complex genetics of autism spectrum disorders. Evan Eichler and his colleagues at the University of Washington plan a broad and systematic approach to uncover autism-linked genes by scouring the fragile regions of DNA for sporadic, non-inherited deletions or duplications.

Based on a genome-wide association study, Mark Daly of Massachusetts General Hospital and his colleagues reported in 2008 that genetic variation in the 16p11.2 chromosomal region is a major risk factor for autism. Daly and colleagues also uncovered more than 100 other rare genetic variations that appear to contribute to risk of autism, but these polymorphisms need further confirmation to prove an association with the disorder. Taking advantage of the SFARI Simplex Collection, the researchers plan to intensively sequence the implicated regions to find rare point mutations that would not be detectable using past or current genome scanning techniques.