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July 28, 2004 — Once you know one Romance language, it’s easier to learn the next. Whether you’re aware of it or not, you already understand the underlying grammar.
Scientists working to understand complex genetic disorders say genetic research works the same way. Once they figure out the genetic ‘grammar’ underlying one complex disorder, it becomes easier to learn how the next one works.
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Last week, the National Alliance for Autism Research (NAAR) announced the launch of the NAAR Autism Genome Project, which the Alliance says is the largest study ever conducted to find the genes associated with inherited risk for autism. As the study proceeds, scientists say it could become a template for other such research in the future.
“I expect you’ll gain some insight about the underlying architecture of the brain,” said Andy Shih, director of research and programs at NAAR. As a result, the progress of studies into complex disorders like autism could gain increasing momentum.
To get a sense of the enormity of the project, consider another recent study. Last week, scientists at the Translational Genomics Institute (TGEN) of Phoenix and the Clinic for Special Children in Strasburg, Pa., announced they had found a genetic basis for one particular form of sudden infant death syndrome, or SIDS.
By comparing DNA from four infants in a small Pennsylvania Amish community, researchers were able to determine the gene responsible for the condition. Although several other genes are known to be associated with SIDS, researchers said this was the first gene identified to cause a primary form of SIDS.
Whereas researchers hunted down a single gene from a small sample in the SIDS study, they will be tackling 6,300 DNA samples from 1,500 families in the autism research.
“Right now we don’t know the common denominators,” Shih said. “They don’t know what they’re looking for, (except that) they’re looking for a pattern.”
Dietrich Stephan, senior investigator and director of the neurogenomics division at TGEN and leader of both the SIDS and autism research teams, said that the autism research community thinks that between 5 and 20 genes are involved, though he cautioned that this was just an estimate.
The area of study has been controversial. Reports have cited a marked increase in autism in recent years. However, different studies have used different methodologies, according to Shih. Moreover, he added that there is no biological definition of the disease. There has been an ongoing debate on the extent that autism is caused by genetics, environmental factors or both.
Shih credited the ongoing debates, an organized parent community and recent technology developments for making the project possible. For example, Stephan estimated that the gene chip used in both studies, the Mapping 10K Array from Affymetrix Inc., has made the work go a hundred times faster than with the previous technology’s rate.
In short, no matter how great the demand, the sheer scale of this study would not have been possible without the 10K array.
The technology is also a validation of Affymetrix’s business model. The 10K array was originally used by Perlegen Sciences Inc., an Affymetrix spinoff, to sequence 50 complete human genomes.
After the 10k array was shown to work well by Perlegen, which used a wafer-scale version of the device, it was packaged into a chip for standard customers, according to Greg Yap, Affymetrix’s senior marketing director for DNA analysis.
Now that the necessary technology is available, Yap said the model whereby patient advocacy groups, doctors, scientists, non-profits and federal agencies collaborate, will also work well for other genetic studies.
In fact, another study is already underway that would not have been feasible without the latest generation of microarrays. Scientists at Rockefeller University have been studying 3,200 people on the island of Kosrae in Micronesia to discover genetic variations associated with obesity, high blood pressure and diabetes.
Prior to World War II, Yap said, obesity was virtually nonexistent on the island. But after the war many people developed obesity when the traditional island diet changed to higher-fat foods. Researchers are looking for genetic patterns that distinguish subjects with obesity.
Despite high hopes, a long road lies ahead. Autism researchers hope to have data ready for interpretation by the end of 2004, according to Shih, who said he hopes that the group will be preparing for publication within a year of starting the project. After that, he said, it is likely to take four to five years to understand the details.
“It’s like drilling down with a map,” he explained. First you locate the state, then the city, then the town, until at last you find the individual house — or, as the case may be, houses — that you are looking for.