Overall, more than 20 genes and chromosomal regions are known to cause autism when defective but together, these account for only around 10 percent of cases. Dr. Zoghbi and her colleagues are developing a strategy to uncover the genes involved in the remaining majority of autism cases. The researchers reason that autism-related molecular pathways, such as those involved in the functioning of neuronal networks, are a good starting point in their search for potential autism genes. They have assembled a collection of proteins known to be implicated in these pathways and then screened a library of human brain proteins to find other proteins that interact with those in the collection. After ruling out a number of genes involved in disorders whose symptoms are distinct from those of autism, Zoghbi and collaborator Dr. Gibbs propose to sequence the remaining 500 genes in DNA samples from individuals with autism enrolled in the Simons Simplex Collection. They plan to screen the samples for chromosomal deletions or duplications and to analyze the DNA from the individuals' parents. Using these genetic techniques, Zoghbi and colleagues aim to pinpoint genes in which sequence variations or defects are linked to autism and determine whether these events are heritable or occur spontaneously.