Autism -- or more precisely autism spectrum disorders (ASDs) -- represents a broad group of developmental disorders ranging from autistic disorder, which is severe, to the milder Asperger syndrome. Across the spectrum, although to varying degrees, the ASDs are characterized by impaired social interactions, problems with verbal and nonverbal communication, and repetitive behaviors, or severely limited activities and interests. Once thought uncommon, ASDs are now understood to affect an estimated 3.4 of every 1,000 children aged 3-10. The risk is 3-4 times higher in males than females, although one rare ASD, Rett syndrome, affects females almost exclusively.
CSHL scientists are employing new technologies and software developed at the Lab to scan and analyze genomes in an effort to understand the genetics of autism. Discoveries at CSHL about variations in human genome structure have been especially revealing. Pathbreaking work has brought to light the previously unrecognized importance in autism of spontaneous gene copy-number variations (CNVs) in the germ line. A team of CSHL scientists is attempting to make mouse models of the illness based on a mutation of particular interest on chromosome 16. At the same time, statistical analysis of the incidence of autism in families has provided evidence for one CSHL scientist’s proposed “unified theory” of autism’s genetic basis, which helps to account, among other things, for the sharp gender skew in the distribution of ASDs. Other CSHL labs are pursuing knowledge about the development, structure and function of neural circuits in the brain – studies that are helping to reveal what goes awry in the autistic brain.
Some important research highlights:
In 2004, Dr. Michael Wigler uses genome-scanning technology to demonstrate the ubiquity in humans of a type of genomic mutation called copy-number variation, or CNV. He and colleagues soon undertake to identify genetic changes that have a role in the causation of neuropsychiatric disorders.
In 2007, a team led by Dr. Wigler finds a distinction between heritable and sporadic forms of autism. The key evidence is the discovery that many children with autism have spontaneous mutations in their DNA and that this occurs more often in the sporadic cases than in either familial cases or in healthy children.
Also in 2007, Dr. Wigler and colleagues including Dr. Kenny Ye of Albert Einstein College of Medicine proposed a “unified theory” of autism’s genetic causation. The model, which builds on recent CSHL findings that spontaneous mutation is frequent in sporadic autism and less frequent in children from high risk families, proposes two prominent risk classes for families affected by autism, and helps to explain the gender distribution of the illness.
Learn more about autism-related research at CSHL: