A Massive Search for Autism Genes Begins

Continued from page 1

The new study will use a chip developed by Affymetrix, a DNA-analysis company based in Santa Clara, CA, that searches for 500,000 specific genetic variations, or SNPs (single nucleotide polymorphisms), in a single experiment. Scientists will analyze the DNA of 3,700 autistic people and their families for SNPs that appear more frequently in those with the disorder, compared with nonaffected participants in the study.

Because the chip detects so many SNPs, almost every one can be traced to a location near or within a specific gene in the genome. "Each hit can get you right to the gene of interest," says Tanzi. "That's really a quantum leap forward, like going from Little League to the major leagues."

As soon as the researchers find a candidate list of genes, which they think could happen in as little as six months, they will make the data publicly available, allowing other scientists to study the genes and their role in autism. Experts expect the project to point toward genes and pathways no one has ever considered in autism -- pathways that, in fact, might lie at the root of the disorder.

Indeed, studies using advanced DNA chips have uncovered surprising causes of other diseases. According to Daly, a similar study of age-related macular degeneration (the leading cause of blindness in people older than 55 in the United States) highlighted genes involved in the function of the immune system rather than genes specific to the eyes or brain. "The genetics led us to a biological pathway that people had not been focused on," says Daly. "It gives a foundation that allows the research community to focus on what's really causal, rather than simply an effect of the disease."

Other planned or ongoing studies that use the new Affymetrix chip, which went on the market last September, are targeting disorders including diabetes, obesity, and Alzheimer's disease. Tanzi has already completed initial analysis in Alzheimer's patients and expects to have a list of candidate genes in a month.

So will these gene chips finally force complex genetic diseases to surrender to DNA analysis? "I'm very confident we're going to find genes associated with complex disorders," says Daly. "I'm equally confident we won't find all of them, maybe not even a majority. But for neuropsychiatric disorders, such as autism or schizophrenia, where we don't know any of the genes or have any insight into the causal basis of the disorder, uncovering even a single gene could be transforming."

For those facing the daily mysteries of a disease like autism, that is welcome news. "This is really on the cutting edge of technology," says Andy Shih, chief scientific officer at Autism Speaks, an advocacy group based in New York City. "The fact that people are willing to apply this technology to autism is exciting."