Public Release:  In autism, it depends on which parent passes on the genetic abnormality

Duke University Medical Center

PHILADELPHIA -- While it has been known that genetic abnormalities are implicated in susceptibility to autism, new research by Duke University Medical Center researchers has added another variable - the particular parent who contributes the defective gene can determine whether or not the child acquires autism.

The researchers point out that autism is an extremely complex disease with a wide spectrum of behavioral manifestations and it is likely that other genes or environmental factors are involved. However, their sophisticated genetic analysis has for the first time suggested that a phenomenon known as genetic imprinting is at work in autism and that it appears to be an important factor in the disorder.

Genetic imprinting is a process by which a gene's expression is governed solely by which parent donates the gene copy, rather than by the classic laws of Mendelian genetics, in which genes are either dominant or recessive. Imprinted genes typically become inactivated, or turned off, during the development of egg or sperm cells, or shortly after fertilization.

"Autism is not a simple genetic disease, caused by the presence or absence of a single gene," said Allison Ashley-Koch, a post-doctoral fellow at Duke's Center for Human Genetics. "We're finding that it is much more complex."

Ashley-Koch prepared the results of the Duke study for presentation Friday at the annual scientific sessions of the American Society for Human Genetics. The autism research is sponsored by numerous grants from the National Institutes of Health.

"We've always known that imprinting exists - there are examples in less complicated organisms," said Margaret Pericak-Vance, director of Duke's Center for Human Genetics (CHG) and senior autism researcher. "Now, with the new technologies in genomics, we can look at more complex inheritance patterns in human disorders. These findings suggest a possible mechanism behind the underlying genetic cause of autism."

The researchers examined 82 families who had at least two family members afflicted with some form of autism. By applying the latest genetic sleuthing techniques, the researchers were able to demonstrate that imprinted genes may be at work. Specifically, they found preliminary data suggesting a paternal effect on chromosome 7 and a maternal effect on chromosome 15.

Genetic imprinting has recently been shown to be involved in several rare human disorders, including Prader-Willi Syndrome and Angelman syndrome, which both can produce autism-like symptoms. All are considered neurodevelopmental disorders.

"Many children with these syndromes have altered genes in the same region of chromosome 15 that we are looking at in autism," Pericak-Vance noted. "This area of chromosome 15 is highly unstable and prone to genetic rearrangement."

Autism is a complex disease that affects two to 10 per 10,000 people, making it the third most common developmental disability - almost as common as Down syndrome. But because of the broad differences in severity of the disease, doctors have difficulty diagnosing it with certainty. Some children simply talk later than normal, while others have severe withdrawal and self-destructive patterns of repetitive head banging and difficulty sleeping or other manifestations.

Doctors believe that the disorder begins during development of the brain, possibly even before birth, and that the change prevents affected people from properly processing sensory information from their environment.

"Once we better understand the genetic factors involved in autism, genetic testing can theoretically be offered to families at risk," Ashley-Koch said. "In addition, identification of such genes will pave the way for development of therapies to improve the quality of life for these children."

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The team included the following investigators, from Duke: Marisa Menold, Kimberly Joyner, Shonda Mason, Christie Poole, Shannon Donnelly, Chantelle Wolpert, Dr. Robert DeLong, Dr. Jeffery Vance and Dr. John Gilbert. Other collaborators include: Sarah Ravan, Ruth Abramson, Michael Cuccaro and Harry Wright, all from the University of South Carolina; Lennord von Wendt from the Helsinki University Central Hospital, Finland; and Cate McCain from the University of New Mexico.

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