Different Genes May Cause Autism In Boys And Girls

Like detectives trying to solve a murder case, researchers searching for the biological cause of autism have come up with some surprising suspects.

They've found that different genes may be responsible for causing autism in boys than in girls.

In addition, the researchers also have discovered that other genes may play a role in the early onset form of the developmental disorder and in the recently verified regression, or late onset, type of autism, according to a new study published today in the online edition of the journal Molecular Genetics.

The study also provides new evidence for the idea that multiple genes contribute to autism, said lead author Gerard Schellenberg, a researcher at the Puget Sound Veterans Affairs Medical Center and a research professor of medicine at the University of Washington. The research team was headed by Schellenberg, Ellen Wijsman, a UW research professor of medical genetics and Geraldine Dawson, director of the UW's Autism Center.

"It is highly unlikely that there is only one gene responsible for autism," said Schellenberg. "There may be four to six major genes and 20 to 30 others that might contribute to autism to a lesser degree.

"If an individual only gets three high-risk variants of these genes, it could mean a less-severe form of autism. And because autism is rarer in females, it may take more risk genes for a female to have autism. There also is the possibility that there might be a biological difference in autism for females versus males," he said.

"What is meaningful is that we have found evidence for two genetic subtypes of autism, male versus female and early versus late onset," added Geraldine Dawson, a professor of psychology. "This is a critical piece of information. With Alzheimer's disease research, one big breakthrough was segregating the late and early onset forms of the disease, and this led to important genetic discoveries."

Schellenberg said the study came up with "strong support" for an autism gene on chromosome 7 and "less, but still compelling evidence" for genes on chromosomes 3, 4 and 11. These results confirm some data from previous studies, particularly involving chromosome 7.

The search for autism genes is part of a long-term Autism Center effort to uncover the genetic and neurobiological causes of autism. To find regions of the human genome that contain autism genes, the researchers scanned the DNA of 169 families that had at least two siblings who met the strict criteria for autism. They also scanned the DNA of another 54 families that, in addition to having individuals with strictly defined autism, also included members who had less severe forms of the disorder, such as Asperger syndrome.

"We have been working almost 10 years to get to this point," said Schellenberg. "If we can find and confirm that a particular gene is involved in autism the field will explode. We have to find a gene so that molecular biology can be defined and we can understand what's inside autism. Until that happens, we are dancing on the outside."

Dawson said the researchers are looking for autism susceptibility genes, ones that heighten the risk of an individual getting autism, just as there are genes that raise the chances of getting breast cancer.

"Once we discover these susceptibility genes, we can immediately screen infants to identify those at risk early in life. Early identification can lead to early intervention, which could have a much more dramatic effect.

"Also, when a gene is discovered, you discover the underlying biology of autism at the molecular level. Once you understand the biology you can develop a prevention strategy including medical approaches. Genetic research is a good strategy for eventually designing effective medical treatments for autism," she said.


The research is part of the National Institute of Child Health and Human Development Collaborative Program of Excellence in Autism. The research is ongoing and families who have more than one child of any age with an autism spectrum disorder who are interested in participating in the UW genetics study can call toll free 1-800-994-9701.

Co-authors of the paper are Yun Ju Sung, Annette Estes, Jeff Munson, Elisabeth Rosenthal and Joseph Rothstein of the University of Washington; Leslie Leong and Chang-En Yu of the Puget Sound Veterans Affairs Medical Center; Patricia Rodier of the University of Rochester Medical Center; M. Ann Spencer of the University of California, Irvine; Nancy Minshew of the University of Pittsburgh; and William McMahon of the University of Utah.

For more information, contact Schellenberg zachdad@u.washington.edu or Dawson dawson@u.washington.edu

Contact: Joel Schwarz
University of Washington



Study Provides Evidence That Autism Affects Functioning Of Entire Brain

A recent study provides evidence that autism affects the functioning of virtually the entire brain, and is not limited to the brain areas involved with social interactions, communication behaviors, and reasoning abilities, as had been previously thought. The study, conducted by scientists in a research network supported by the National Institutes of Health (NIH), found that autism also affects a broad array of skills and abilities, including those involved with sensory perception, movement, and memory.

The findings, appearing in the August Child Neuropsychology, strongly suggest that autism is a disorder in which the various parts of the brain have difficulty working together to accomplish complex tasks.

The study was conducted by researchers in the Collaborative Program of Excellence in Autism (CPEA), a research network funded by two components of the NIH, the National Institute of Child Health and Human Development and the National Institute on Deafness and Other Communication Disorders.

"These findings suggest that further understanding of autism will likely come not from the study of factors affecting one brain area or system, but from studying factors affecting many systems," said the director of NICHD, Duane Alexander, M.D.

People with autism tend to display 3 characteristic behaviors, which are the basis of the diagnosis of autism, explained the study's senior author, Nancy Minshew, M.D., Professor of Psychiatry and Neurology at the University of Pittsburgh School of Medicine. These behaviors involve difficulty interacting socially, problems with verbal and non-verbal communications, and repetitive behaviors or narrow, obsessive interests. Traditionally, Dr. Minshew said, researchers studying autism have concentrated on these behavioral areas.

Within the last 20 years, however, researchers began studying other aspects of thinking and brain functioning in autism, discovering that people with autism have difficulty in many other areas, including balance, movement, memory, and visual perception skills.

In the current study, Dr. Minshew and her colleagues administered a comprehensive array of neuropsychological tests to a group of children with autism. The researchers tested 56 autistic children, and compared their responses to those of 56 children who did not have autism. The children with autism were classified as having higher functioning autism--an I.Q. of 80 or above, and the ability to speak, read, and write. All of the children in the study ranged in age from 8 to 15 years. The purpose of the test array, Dr. Minshew said, was to determine whether there were any patterns in mental functioning unique to autism.

"We set out to find commonalities across a broad range of measures, so that we could make inferences about what's going on in the brain," Dr. Minshew said.

The researchers found that, across the entire series of tests, the children with autism performed as well as--and in some instances even better than--the other children on measures of basic functioning. Uniformly, however, they had trouble with complex tasks.

For example, regarding visual and spatial skills, the children with autism were very good at finding small objects in a cluttered visual field, on tasks like finding Waldo in the "Where's Waldo" picture books series. However, when asked to perform a complex task, like telling the difference between the faces of similar looking people, they had great difficulty.

Although their memory for the detail in a story was phenomenal, the children with autism had great difficulty comprehending the story. Many were highly proficient at spelling and had a good command of grammar, but had difficulty understanding complex figures of speech, like idioms and metaphors.

"We see this with our patients," Dr. Minshew said. "If you use an expression like 'hop to it,' a child with autism may literally hop."

Other complex tasks were also difficult for them. The children with autism either had poor handwriting, or wrote very slowly. Many had difficulty tying their shoes and with using scissors.

"These findings show that you can't compartmentalize autism under three basic areas," Dr. Minshew said. "It's much more complex than that."

Dr. Minshew explained that the major implication of the finding is that when seeking to understand autism, researchers need to look for a cause or causes that affect multiple brain areas, rather than limiting their search to brain areas dealing with the three characteristic behaviors involving social interactions, communication, and repetitive behaviors or obsessive interests.

"Our paper strongly suggests that autism is not primarily a disorder of social interaction, but a global disorder affecting how the brain processes the information it receives--especially when the information becomes complicated."

In previous research with an imaging technology known as functional magnetic resonance imaging, or fMRI, Dr. Minshew and her coworkers determined that adults with autism have abnormalities in the neurological wiring through which brain areas communicate. In those studies, the researchers found that people with autism had difficulty performing certain complex tasks that involved brain areas working together. (This research is described in previous releases, http://www.nichd.nih.gov/, and http://www.nichd.nih.gov/new/releases/autism_brain_structure.cfm.)

Dr. Minshew said that such abnormalities in brain circuitry provide the most likely explanation for why the children with autism in the current study have difficulty with complex tasks that require coordination among brain regions but do well on tasks that require only one region of the brain at a time.

The researchers undertook the current study as a follow up to an earlier study they did of adults with autism. The researchers studied children to determine if the features of autism were consistent throughout life, or changed as people with autism grow older. For the most part, the current study revealed that both adults and children with autism experience the same kinds of difficulties with complex tasks.

One difference is that adults with autism appear to score higher on tests involving sensory interpretation than do children with autism. Such tests would involve identifying a number traced on a finger tip, or identifying an object placed in one's hand without looking at it. Dr. Minshew said that as people with autism grow older, they may have less sensory difficulty than they did as children.

Still, adults with autism fare much worse on tests of complex language and reasoning than do other adults. This gap in complex language and reasoning ability between the two groups is not as pronounced when children with autism are compared to other children. This is because children's brains have not yet developed these skills, Dr. Minshew said. However, the gap widens with time. As typical children get older, they develop these higher order language and reasoning skills while adolescents and adults with autism do not.


The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Institute's Web site at http://www.nichd.nih.gov/.

The National Institutes of Health (NIH) -- The Nation's Medical Research Agency -- includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov/.

Contact: Robert Bock or Marianne Glass Miller
NIH/National Institute of Child Health and Human Development


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