The hunt for the genetic basis of autism may soon be closing in on its elusive target. Scientists at 11 Boston-area institutions, including MIT and the Broad Institute, will use new tools to analyze DNA samples from thousands of autistic people and their families. It is expected to be the largest search to date for the genetic causes of autism and may yield candidate genes in as little as six months.

“This project will allow us to study the genome with an unprecedented level of detail,” says Mark Daly, a researcher at the Broad Institute who is participating in the project. “Once we have an understanding of the genes and causal pathways underlying the disease, we can focus [on] research and development of therapeutics for those genes.”

Scientists know that autism, which occurs in about one in 166 children, has a genetic component; siblings of autistic people have a much higher chance of developing the disorder than the general population. But the disease probably has a number of causes, including environmental influences and multiple genes. As with other complex genetic diseases, pinpointing the genes that increase risk has been enormously difficult.

Previous studies have identified large regions of the genome that appear to contain genetic variations linked to autism. That region might contain hundreds of genes, however, and the limits of DNA-analysis technology have made identifying the specific culprit a challenge. In such situations, scientists usually make a guess based on the known biology of the disease. “It’s very frustrating,” says Rudy Tanzi, a neurologist at Harvard Medical School and a collaborator on the project. “The odds are low that you’ve picked the right gene.”

But scientists can now scan the genome much more thoroughly using newer varieties of gene chips, tiny glass slides coated with particular sequences of DNA that can identify sequences in a sample by binding to them. The latest chips can quickly detect more DNA sequences than ever before – hundreds of thousands of them at a time. “Now we can find diamonds among the glass,” says Tanzi.

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.”