Genetic research reveals pieces of autism puzzle

As the number of children with autism has increased over the past couple of decades, so have efforts to find causes behind this neurodevelopmental disorder. Research published Wednesday provides new clues about genetic glitches that may contribute to the development of autism among children.

Ten years ago, little was known about the role genetics plays in autism. But improved technology has allowed scientists to delve deeply into DNA to search for answers.

"Ten years ago [it was like] we were looking through binoculars, then we were looking at autism through a microscope, and now it's like looking at it in high definition," says Andy Shih, vice president of scientific affairs for the advocacy group Autism Speaks, who was not involved in the research.

Since the first human genome was sequenced in the early 2000s, researchers have had the opportunity to search for genes that cause the disorder, which affects an estimated 1 in 88 children in the United States.

Researchers were originally searching for a single gene that would cause the disorder, but they now believe it's much more likely that there are multiple genetic mutations that put a child at risk. By studying specific areas of the DNA of families that have a child with autism, scientists have identified approximately 1,000 genes that may be involved.

A person's whole genome consists of about 3 billion nucleotides, or “letters,” of DNA. But only 1.5% of it - a portion called the "exome" - produces proteins. The exome also harbors 85% of disease-causing mutations, according to the National Institutes of Health.

Three studies published in the journal Nature this week analyzed the exomes of parents and children with autism and found spontaneous genetic mutations in the exome play a significant role in raising a child's risk of developing autism.

One study looked at 238 families with one child with autism and one child without autism.

"We found ... several sequence changes [mutations] in the base pairs of DNA that are not seen in a parent," says study co-author Dr. Daniel Geschwind, professor of neurology and psychiatry at UCLA School of Medicine. "These mutations are not inherited, but either occur in the mother's egg or father's sperm (before conception) or in the child itself (after conception)."

Geschwind says this new research suggests a child with these mutations "has a much higher chance" of developing a disorder like autism. This research team, led by Dr. Matthew State of Yale University, found at least 14% of those with autism had multiple genetic mutations, which is five times the normal rate, according to the NIH.

Another research team headed by Evan Eichler, a professor of genome studies at the University of Washington, found 39% of spontaneous mutations were likely to increase the risk of autism because they interfere with biological developments that are important for communication in the brain.

Eichler's research also found these spontaneous mutations were "overwhelmingly paternal in origin," suggesting the origin of these mutations are in a father's sperm. This supports previous research that suggested there's an increased risk of a child developing autism if the father is older.

The third study in Nature, led by Mark Daly, associate professor at Harvard Medical School, found many mutations seen in children with autism are not necessarily connected to the disorder. His research found that the mutations that are linked to autism are spread over many genes, and so may not be enough to cause the disorder.

In addition to these three studies, an independent study published in Science Translational Medicine, found a non-protein-producing gene can also contribute to the risk of autism.

"All four of these studies get us closer to understanding the biology of autism," says Daniel Campbell, lead author of the fourth study, and assistant professor of psychiatry and the behavioral sciences at the University of Southern California.

Looking at this research collectively further supports the notion that autism is a neurodevelopmental disorder, and that the disruptions in development that lead to autism are laid down very early in brain formation, says Dr. Bryan King, director of the Seattle Children's Autism Center.

"This [research] is yet another example of how we don't have any single gene that can be connected in a straight line to autism," says King, who wasn't involved in the research.

"There's no one gene that causes autism," says James Sutcliffe, one of Daly's co-authors and an associate professor of molecular physiology, biophysics and psychiatry at Vanderbilt University. "But what these studies do show is that several genetic mutations increase the risk of getting autism and different mutations may affect people in a different way."

Much more research is needed, but ultimately identifying more genetic mutations could pinpoint targets for researchers to focus on to find ways to counteract the developmental disabilities they can cause. Or maybe, in the future, this research could lead to diagnostic tests that could identify children who are at risk for autism so they can get the earliest possible interventions.