Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

New genetic hypothesis for the cause of autism

08.09.2004


A mixed epigenetic and genetic and mixed de novo and inherited model may explain most cases of autism



Researchers have proposed a new hypothesis on the cause of autism, suggesting a mixed epigenetic and genetic and mixed de novo and inherited (MEGDI) model. Their hypothesis, and evidence to support it, will be published September 8, 2004 in the online edition of the American Journal of Medical Genetics Part A, and will be available via Wiley InterScience at http://www.interscience.wiley.com/journal/ajmg.

The role of genetics in autism is believed to be significant because twin studies have found that identical twins, who have the same DNA, are much more likely to share the diagnosis than fraternal twins. However, experts have not yet identified the specific genetic components related to autism, and many experts believe that multiple genes are involved.


Researchers, led by Yong-hui Jiang of Baylor College of Medicine in Houston, propose that most cases of autism can be explained by a complex model for genetic malfunction that may or may not include an altered DNA sequence. Where the DNA sequence is intact, the researchers believe that gene expression could be faulty. They suggest that some of these genetic factors are inherited, and others occur de novo in genes of the autistic person. In this study, they formulate a five-part hypothesis on the cause of autism:

Based on the evidence of parent-of-origin effects, they propose that there is a major epigenetic (related to gene expression, not sequence) component in the etiology of autism involving genetic imprinting. They suggest that epigenetic and genetic factors (both de novo and inherited) cause autism through dysregulation of two or more principal genes, one of which maps within chromosomes 15q11-q13, with the Angelman gene encoding E6-AP ubiquitin-protein ligase (UBE3A) being the strongest candidate in this region

They propose that the dysregulation of UBE3A involves some combination of overexpression, gene silencing, or misexpression of the three potential isoforms of E6-AP. They believe twin data on autism are best explained by de novo defects (epigenetic or genetic) arising in germ cells or in the embryo prior to twinning. They speculate that one or more additional genes whose function affects the role of UBE3A likely participate with the Angelman gene in an oligogenic inheritance model.

The researchers reviewed available evidence and conducted their own investigations to test elements of their hypothesis. For example, from evidence that maternal, but not paternal, inheritance of extra material from chromosome 15 causes autism in a small fraction of cases, they suggest that this chromosome, and more specifically, the gene for Angelman syndrome in this region, plays a greater role in autism than is currently appreciated. They also noted the difference in the effects of a gene depending on which parent transmits it, which strongly suggests an epigenetic effect called genomic imprinting.

The authors do not argue that their data prove the components of the oligogenic hypothesis. They say, rather, that the model is generally compatible with the data presented, it represents some fresh perspectives for autism, and it can be tested in a number of ways. "We believe that this model is highly likely to apply to some small fraction of autism cases," say the authors, "but more importantly and more speculatively, we propose that it will explain the majority of cases of autism."

The oligogenic model does not entirely rule an environmental role in autism. "The epigenetic component of the oligogenic model can be considered in the context of possible environmental factors affecting the risk of de novo imprinting defects. Non-genetic factors could affect the risk for an epigenetic form of autism," the authors conclude.

If the MEGDI model is correct for autism, it could also be relevant to other disorders, such as schizophrenia or bipolar mood disorder that clearly have a genetic component but have resisted understanding despite the completion of the human genome project.

David Greenberg | EurekAlert!
Further information:
http://www.wiley.com
http://www.interscience.wiley.com/journal/ajmg

More articles from Life Sciences:

nachricht Water world
20.11.2017 | Washington University in St. Louis

nachricht Carefully crafted light pulses control neuron activity
20.11.2017 | University of Illinois at Urbana-Champaign

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

Im Focus: Researchers Develop Data Bus for Quantum Computer

The quantum world is fragile; error correction codes are needed to protect the information stored in a quantum object from the deteriorating effects of noise. Quantum physicists in Innsbruck have developed a protocol to pass quantum information between differently encoded building blocks of a future quantum computer, such as processors and memories. Scientists may use this protocol in the future to build a data bus for quantum computers. The researchers have published their work in the journal Nature Communications.

Future quantum computers will be able to solve problems where conventional computers fail today. We are still far away from any large-scale implementation,...

Im Focus: Wrinkles give heat a jolt in pillared graphene

Rice University researchers test 3-D carbon nanostructures' thermal transport abilities

Pillared graphene would transfer heat better if the theoretical material had a few asymmetric junctions that caused wrinkles, according to Rice University...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Antarctic landscape insights keep ice loss forecasts on the radar

20.11.2017 | Earth Sciences

Filling the gap: High-latitude volcanic eruptions also have global impact

20.11.2017 | Earth Sciences

Water world

20.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>