Using recent technological advances in genetics to rapidly acquire data, researchers have linked several genes and chromosomal aberrations to autism. Steve Warren of Emory University and colleagues plan to implement these high-throughput methods to address one mystery of autism: roughly four times as many males as females are affected by the disorder.

Autism arises, at least in part, as a result of poor signaling between neurons, which disrupts the behavioral pathways necessary for social interactions, language development and motor control. At Stanford University, Thomas Südhof and his colleagues plan to study how proteins called neuroligins regulate neuronal signaling, in order to understand their role in those behavioral pathways and in autism.

Viral infection during pregnancy raises the risk of autism in the offspring, suggesting a connection between the maternal immune system and fetal brain development. Paul Patterson of the California Institute of Technology and his colleagues have successfully modeled this scenario in mice. In collaboration with David Amaral’s group at the University of California, Davis, they plan to extend these studies to non-human primates, which are socially and physiologically more similar to humans.

Each person with autism has a unique set of abilities and disabilities, and this heterogeneity has made the finding the genetic causes of the disorder difficult. Daniel Geschwind and his colleagues at the University of California, Los Angeles, plan to look for commonalities in gene expression that might define subgroups of people with autism — information that will aid the search for both the cause of and treatment for autism.

Many children with autism have enlarged brains, often caused by an abnormally high density of neurons in the forebrain. Steven McKnight at The University of Texas Southwestern Medical Center and his colleagues hypothesize that defects in the NPAS1 gene, which acts as a brake on the creation of neurons in the developing brain, predispose individuals to autism.

Although autism is highly heritable, its heterogeneity has challenged gene-finding efforts. Daniel Geschwind and his colleagues at the University of California, Los Angeles, propose to identify the gene networks frequently dysregulated in people with autism, regardless of the underlying mutations.

Genetic studies have identified several loci, or stretches of chromosomal DNA, that are defective in individuals with autism. These loci contain more than one gene, so the next step is to identify the specific genes that are mutated. To that end, Alea Mills and her colleagues at Cold Spring Harbor Laboratory in New York propose to develop a series of mouse models carrying chromosomal defects analogous to those seen in individuals with autism.

Autism is a heritable disease, but the contribution of genetic factors is not straightforward. The symptoms and severity of autism spectrum disorders vary greatly between affected individuals, and relatives often show milder, but related, cognitive and behavioral difficulties. Some genetic defects have been linked to autism, but the resulting phenotypes could be influenced by other factors such as environmental variables and the parent from whom the mutations were inherited.

Numerous genes have been linked to autism, but it is not entirely clear how mutations in individual genes translate to the social deficits seen in people with the disorder. Because the symptoms of autism typically appear during periods of heavy neural development, Mriganka Sur at the Massachusetts Institute of Technology suggests that defects in genes that control early brain development are partly to blame.

The genetics of autism has proven to be as complex as the genetics of other diseases in people. As seen in many human diseases, candidate genes appear to affect a wide range of biological processes, but not very consistently.