Roughly one percent of cases of autism are associated with deletions within a single region of chromosome 16, which contains nearly 30 genes. It is unclear which, and how many, of these genes are crucial in this association. Hazel Sive at the Whitehead Institute of Biomedical Research and her colleagues plan to determine which of these genes regulate brain development in zebrafish, in order to identify the genes that may contribute to the development of autism spectrum disorders.

Autism arises from mutations in the genome, but several studies have shown that many of these mutations occur de novo — that is, they are non-inherited mutations introduced during the parents’ gamete production. Jay Gingrich at the New York State Psychiatric Institute and his colleagues plan to study a mouse model of autism to investigate whether advanced paternal age is linked to a higher frequency of genomic aberrations.

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.

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.

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.