More than one ball in the air pg. 3
The findings, published in Nature in 1977, “brought to a clear end the period of time when people thought of autism as something that was caused by parents,” says Folstein, professor of Psychiatry at Tufts-New England Medical Center. “The study was also the impetus for many other family studies of autism.”
Folstein and Rutter’s initial twin study and others since then offer the most compelling evidence for the high heritability of autism. Identical twins have a greater than 50 percent chance of both being autistic. The relative risk to siblings—nine to 45 times the risk to the general population—is higher than many other complex disorders like diabetes, asthma, and schizophrenia. But the genetic factors contributing to autism have remained elusive.
Jonathan L. Haines, Ph.D., director of the Vanderbilt Center for Human Genetics Research, began collaborating with Folstein in the mid-1990s. Compared to other diseases and disorders he was working on at the time, “it looked like the genetics of autism should be relatively easy to solve,” he recalls. “Big mistake.”
“The data are suggesting that there are many genes and that they are probably interacting to cause this disorder,” Haines says. “It’s incredibly complex.” That makes sense, he adds, given the sheer variation in the expression of the disorder, in the symptoms that children have.
To search for those proverbial needles in the haystack—the small group of genes that contributes to autism out of the 30,000 or so genes that make up the human genome—investigators use a combination of two approaches. They scan randomly through the entire genome in families with at least two affected individuals, called multiplex families, looking for DNA regions with high similarity in the people with autism. And they examine “candidate genes,” which because of their biological function are suspected of playing a role in the developmental changes that cause autism.
The approaches have pointed to many different chromosomal regions—areas on chromosomes 2, 3, 7, 15, and 19 that are linked to the disorder in some sets of families—and to some candidate genes. “There’s a lot of disagreement about those regions, and there are no confirmed genes,” Haines says. “No one’s been able to say, ‘This is a gene that causes or influences autism.’
“One could argue that the field is in a great state of confusion right now,” he adds. “But out of that confusion is going to come some real progress in the next year or two.”
The power of genetics
One reason for Haines’ optimism: the development of the Autism Genome Project, a consortium of autism genetics researchers promoted by the National Alliance for Autism Research. If NAAR, a parent-founded advocacy group, is able to secure funding for the giant genetics initiative, up to 1,200 multiplex families will be available for study.