The first results from a scan of the world's largest collection of DNA samples from families affected by autism point to two new genetic links that may predispose people to the brain disorder. The study's findings appear in the Feb. 18 online edition of the journal Nature Genetics.
The five-year study was led by the Autism Genome Project, an international consortium of scientists from 50 institutions in 19 countries. Founded in 2002 with funding from the nonprofit Autism Speaks and the National Institutes of Health, the group shared DNA samples, data and expertise in a coordinated effort to identify autism-susceptibility genes.
"This degree of collaboration is an unprecedented effort in autism research and demonstrates that a genetic approach is a powerful way to deepen understanding of the disease," said Dr. Daniel Geschwind, director of the Center for Autism Research and Treatment at the Semel Institute for Neuroscience and Human Behavior at UCLA, one of the study's 13 research centers.
"This large-scale study reveals that autism is an extremely diverse condition," Geschwind said. "Our findings suggest that autism has numerous genetic origins rather than a single or few major causes."
The consortium used gene chip technology to search for genetic commonality in autistic individuals from nearly 1,200 families. The scientists also scanned DNA from these families for variations in gene copy numbers — tiny genomic insertions and deletions that scientists believe may be involved with autism.
"The large number of families in this study permitted us to organize autistic children with similar features of this disorder into smaller groups, where gene linkages may be more easily detected," said Rita Cantor, professor of human genetics at the David Geffen School of Medicine at UCLA.
Results of the two-pronged approach implicated both a previously unidentified region of chromosome 11 and neurexin 1, a member of a gene family believed to play a key role in communication between brain cells. The neurexin finding highlighted a group of brain cells called glutamate neurons and the genes affecting their development and function, suggesting that they play a critical role in autism spectrum disorders.
"We are excited by the results from this large-scale study," said Dr. Stanley Nelson, professor of human genetics at the Geffen School of Medicine, "At the same time, we must greatly increase the number of autistic persons in our genetic analysis in order to fully describe heredity's role in the disease."
"We hope that identifying these genes will provide new insights into what underlies autism," Geschwind said. "We are optimistic that this approach will lead to improved interventions for autistic children and better quality of life for their families."
In 1997, the citizens group Cure Autism Now (CAN) created a gene bank in order to advance genetic research on autism. UCLA partnered with CAN to add more than 400 families to the bank, known as the Autism Genetic Resource Exchange. The gene bank contributed one-third of the clinical data and samples analyzed by the Autism Genome Project in this study. (Earlier this month, CAN and Autism Speaks merged, pooling their efforts to fund and advance autism research.)
The UCLA families who participated had more than one member diagnosed with one of three genetically related autism spectrum disorders: autism, pervasive developmental disorder or Asperger's syndrome.
Autism is a complex brain disorder that strikes in early childhood, often affecting children as young as 2 or 3. The condition disrupts a child's ability to communicate and develop social relationships and is often accompanied by acute behavioral challenges. While the cause remains unknown, scientists suspect the disease is highly hereditary.
Citing autism as a national public health crisis, the Centers for Disease Control and Prevention report that one in 150 American children is diagnosed with an autism spectrum disorder. Affecting four times as many boys as girls, the diagnosis of autism has expanded tenfold in the last decade.
The UCLA Center for Autism Research and Treatment provides diagnosis, family counseling and treatment for patients with autism. Its research focuses on understanding the origins of the disorder's social, communicative and language deficits, and designing and testing new treatments to help autistic children and adults. The center also centralizes autism resources at UCLA and builds partnerships within the autism community.
UCLA is one of eight centers in the National Institutes of Health-funded Studies to Advance Autism Research and Treatment network and one of the NIH's 10 original Collaborative Programs for Excellence in Autism. For more information, visit http://www.autism.ucla.edu.