Advanced maternal and paternal age have been reported as risk factors for autism spectrum disorders. In general, the genetic quality of eggs and sperm declines over time, reducing the chance of older parents to produce normal offspring. Copy-number variation (CNV) — a type of genetic alteration commonly associated with autism spectrum disorder — is thought to be one of the most common problems with the quality of eggs or sperm in older individuals.

Autism spectrum disorders are heritable, and chromosomal defects are thought to play a role in their development. In a 2008 study, a group of researchers, including James F. Gusella of Massachusetts General Hospital, discovered that a stretch of DNA containing several genes is missing from chromosome 16 in about one percent of people affected or suspected to be affected with autism. The researchers hope to identify the specific genes located in this chromosomal region that play a role in causing autism.

Small variations in the DNA sequence of a gene, called polymorphisms, are known to have an impact on normal and disease phenotypes. Some polymorphisms change the length or makeup of the resulting protein, whereas others interfere with binding sites for molecules that regulate the gene’s expression.

Analyzing genetics using the tissues of people with autism can provide deeper insight into the disorder than performing genetic techniques on DNA samples alone. Arthur Beaudet and his colleagues at Baylor College of Medicine in Houston propose two projects that examine autism genetics in the context of the physiology of the disorder.

For years, autism has been noted in individuals with tuberous sclerosis, leading researchers to speculate that the two disorders may develop after troubles in the same biological pathway. Vijaya Ramesh and her colleagues at Massachusetts General Hospital are pursuing this lead by investigating whether genes linked to tuberous sclerosis are also associated with autism spectrum disorders.

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.