Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New genetic ‘fishing net’ harvests elusive autism gene

07.02.2003


Duke University Medical Center researchers have developed a new statistical genetic "fishing net" that they have cast into a sea of complex genetic data on autistic children to harvest an elusive autism gene.



Moreover, the researchers said that the success of the approach will be broadly applicable to studying genetic risk factors for other complex genetic diseases, such as hypertension, diabetes and multiple sclerosis.

In this case, the gene, which encodes part of a brain neurotransmitter docking station called the gamma-Aminobutyric Acid Receptor beta3-subunit (GABRB3), has been implicated in autism previously, but never positively linked to the disease. Their findings will be published in the March 2003 issue of the American Journal of Human Genetics and is now available on the Web at http://www.journals.uchicago.edu/AJHG/journal/issues/v72n3/024607/024607.html.


"Many research groups have been actively looking for genetic risk factors that can lead to autism, but without much success," said Margaret Pericak-Vance, Ph.D., director of the Duke Center for Human Genetics and lead investigator of the study.

Autism is the common term that encompasses an overlapping group of complex developmental disorders that are diagnosed in about one in 1,000 children under the age of 3. Each autistic child has a unique set of characteristics that affect his or her behavior, communication skills and ability to interact with others. It is the very diverse, complex nature of autism that has made it so difficult to locate distinct genetic risk factors, said Pericak-Vance.

After several genetic studies turned up only a few vague genetic clues, the research team decided a new approach was needed. Pericak-Vance hypothesized that grouping patients with similar traits together statistically might enhance the scientists’ ability to distinguish relevant genetic risk factors. To provide guidance, the scientists turned to Michael Cuccaro, Ph.D., a clinical child psychologist at Duke with extensive experience diagnosing and treating autism. Cuccaro noticed that some but not all autistic children exhibit repetitive compulsions and extreme difficulty with changes to their daily routine. This character trait -- defined by Cuccaro as "insistence on sameness" or "IS" -- helped the research team identify a subset of autism family data to study in more detail.

Researchers, led by Yujun Shao, Ph.D., a genetic epidemiologist at Duke, reorganized data collected from families in which more than one child is affected by autism and grouped together all the families that reported their autistic child had difficulty with change.

Cuccaro’s theory that autistic children could be subdivided into at least two groups gave the team of scientists from Duke and the University of South Carolina an opportunity to test a new statistical method, called "ordered subset analysis," developed by Elizabeth Hauser, Ph.D., assistant research professor of medicine at Duke. This new genetic fishing net allows scientists to sift through complex genetic data and extract genetic risk factors that affect only some of the total group.

In this case, when the researchers applied the new test only to those families whose children scored high in the IS category, they discovered a strong link to the GABRB3 gene on chromosome 15q, where no such link had appeared before.

"This is the first successful application of ordered subset analysis to help us pinpoint a genetic risk factor that would be missed by looking at the larger group." said Pericak-Vance.

The researchers emphasize that this discovery is only the first step in understanding how the GABRB3 gene, or others genes in the same region of chromosome 15 might be involved in autism. Another clue may be gained from previous research that has shown the same area on chromosome 15 is just as responsible for Angelman Syndrome and Prader-Willi Syndrome -- two genetic disorders in which a subset of affected children also exhibit repetitive behavior. Additional research will be necessary to understand how defects in the GABRB3 gene might contribute to autistic disorder, and how other genes or environmental factors also play a role.

"In the short term, however, I think what this will allow us to do is encourage clinicians and researchers working with autistic children to think about autism as consisting of different types or subgroups and not a one-dimensional disorder," said Cuccaro. "I think that subgrouping, over time, will allow us to develop a better understanding of how to treat each individual with autism."

This is a case, said Cuccaro, where identifying subsets of patients based on clinical observations has resulted in a significant neurobiological finding, and it perhaps is pointing a way to bring clinical observations to bear on complex genetic problems.

"The genomic revolution has given us a tremendous wealth of information in terms of a road map and markers for finding disease genes," said Pericak-Vance. "Now, we need to be able to look at complex clinical information and come up with methods that can help us dissect diseases that have multiple risk factors. This new statistical test will allow us to find meaningful genetic risk factors that are diluted out when tested as part of a larger heterogeneous group."


Members of the research team also included Marissa Menold, Chantelle Wolpert, Leigh Elston, Karen Decena, Shannon Donnelly, Robert DeLong, M.D., and John Gilbert, Ph.D., of Duke; and Sarah Ravan, Ruth Abramson and Harry Wright, M.D., of the W.S. Hall Psychiatric Institute at the University of South Carolina. The research was supported by grants from the National Institutes of Health and the National Alliance of Autism Research.

Richard Puff | EurekAlert!
Further information:
http://dukemednews.org/news/article.php?id=6385
http://www.journals.uchicago.edu/AJHG/journal/issues/v72n3/024607/024607.html

More articles from Life Sciences:

nachricht A novel socio-ecological approach helps identifying suitable wolf habitats
17.02.2017 | Universität Zürich

nachricht New, ultra-flexible probes form reliable, scar-free integration with the brain
16.02.2017 | University of Texas at Austin

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Breakthrough with a chain of gold atoms

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport

Im Focus: DNA repair: a new letter in the cell alphabet

Results reveal how discoveries may be hidden in scientific “blind spots”

Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...

Im Focus: Dresdner scientists print tomorrow’s world

The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.

The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...

Im Focus: Mimicking nature's cellular architectures via 3-D printing

Research offers new level of control over the structure of 3-D printed materials

Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...

Im Focus: Three Magnetic States for Each Hole

Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".

Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Booth and panel discussion – The Lindau Nobel Laureate Meetings at the AAAS 2017 Annual Meeting

13.02.2017 | Event News

Complex Loading versus Hidden Reserves

10.02.2017 | Event News

International Conference on Crystal Growth in Freiburg

09.02.2017 | Event News

 
Latest News

Biocompatible 3-D tracking system has potential to improve robot-assisted surgery

17.02.2017 | Medical Engineering

Real-time MRI analysis powered by supercomputers

17.02.2017 | Medical Engineering

Antibiotic effective against drug-resistant bacteria in pediatric skin infections

17.02.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>