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.

A well-characterized microdeletion in the 22q11.2 chromosomal region is known to be associated with schizophrenia. There is growing evidence that duplications at this locus are also associated with autism. Joseph Gogos and his colleagues at Columbia University in New York have been studying the chain of molecular and cellular events arising from copy number variants (CNVs) at this locus, which may lead to altered brain connectivity.

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.

The relationship between genetics and autism is not always straightforward, but some autism spectrum disorders are known to be caused by defects in a single gene. These simpler cases give researchers the opportunity to create animal models with the genetic defect and use them to test hypotheses about the mechanisms at work in autism.

Appropriate social behavior requires a fine-tuned ability to perceive other people’s actions. Human movement is a rich source of social information. The ways in which people move tell us volumes about their intentions and emotions. Maggie Shiffrar and her colleagues at Rutgers University in New Jersey set out to determine how, and how well, people with autism perceive human movement.

Individuals with autism often experience difficulties with day-to-day interaction and communication, such as interpreting body language, reading facial expressions and understanding others’ thoughts and desires. Although they vary in severity and manifestation, these problems may reflect a fundamental deficit in “theory of mind” — the ability to deduce other people’s beliefs and intentions.

Current genetic evidence links autism with defects in signaling between brain cells, or neurons, particularly at specialized regions of the neurons known as synapses. Bernardo Sabatini and his colleagues at Harvard Medical School plan to study how neuron activity affects synapse formation, focusing on the roles of three autism-associated proteins, which are members of the Shank, neurexin and neuregulin families.

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.

Multiple lines of converging evidence document brain enlargement in autism. Magnetic resonance imaging (MRI) studies have revealed generalized enlargement in the cerebral cortex and some subcortical structures by the age of 2 years. Studies of head circumference among high-risk infants suggest that brain overgrowth begins at 6-12 months, and behavioral studies of infants suggest that the defining features of autism generally appear by 12 months of age.