Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Risk of autism tied to genes that influence brain cell connections

29.04.2009
In three studies, including the most comprehensive study of autism genetics to date, investigators funded in part by the National Institutes of Health have identified common and rare genetic factors that affect the risk of autism spectrum disorders. The results point to the importance of genes that are involved in forming and maintaining the connections between brain cells.

"These findings establish that genetic factors play a strong role in autism spectrum disorder," says Acting NIH Director Raynard Kington, M.D., Ph.D. "Detailed analysis of the genes and how they affect brain development is likely to yield better strategies for diagnosing and treating children with autism."

Autism spectrum disorders (ASD) comprise a group of disorders with core symptoms that include social interaction problems, poor verbal and nonverbal communication and repetitive behaviors. These disorders range from severe (autism) to mild (Asperger's syndrome), and in total affect some 1 in 150 American children, about three-quarters of whom are boys. Researchers theorize that the social parts of the brain are underdeveloped in ASD.

"Previous studies have suggested that autism is a developmental disorder resulting from abnormal connections in the brain. These three studies suggest some of the genetic factors which might lead to abnormal connectivity," says Thomas Insel, M.D., director of NIH's National Institute of Mental Health (NIMH).

The studies were funded in part by the NIMH, the National Institute of Neurological Disorders and Stroke (NINDS), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Institute on Deafness and Other Communication Disorders (NIDCD) and the National Center for Research Resources (NCRR), all components of NIH.

All three studies were genome-wide association studies, which are undertaken to find clues about the causes of complex disorders. Typically, these studies involve scanning the genome – the entire set of DNA – for small differences between people who have a disorder and people who do not.

The largest study, reported in Nature, involved more than 10,000 subjects, including individuals with ASD, their family members and other volunteers from across the U.S. The study was led by Hakon Hakonarson, M.D., Ph.D., a professor at the University of Pennsylvania School of Medicine and director of the Center for Applied Genomics at The Children's Hospital of Philadelphia. Among other principal investigators on the study were Gerard D. Schellenberg, Ph.D., also a professor at the University of Pennsylvania School of Medicine; and Daniel Geschwind, M.D., Ph.D., a professor at the University of California, Los Angeles and director of UCLA's Center for Autism Research and Treatment; and Margaret Pericak-Vance, Ph.D., a professor at the University of Miami Miller School of Medicine and director of the Miami Institute for Human Genomics, who also led an independent study that generated similar results.

Major funding for Dr. Hakonarson's work came from The Children's Hospital of Philadelphia. Dr. Pericak-Vance's work was supported in part by the Hussman Foundation. The DNA samples came from a repository called the Autism Genetic Resource Exchange (AGRE), and from subjects recruited at clinics in Philadelphia, Miami, Los Angeles and other sites. AGRE is run by Autism Speaks, with partial support from NIMH.

Previous studies of twins with ASD, other children with ASD and their relatives provided evidence of a strong genetic contribution. Yet until now, only a few genetic risk factors had been identified, and most of those turned out to be rare, with unclear significance for ASD in the general population. Researchers came to realize that the genetics of ASD is complex.

"There are going to be many genes involved in causing autism," says Dr. Hakonarson. "In most cases, it's likely that each gene contributes a small amount of risk, and interacts with other genes and environmental factors to trigger the onset of disease."

In their large study, Dr. Hakonarson and his colleagues found several genetic variants that were commonly associated with ASD, all of them pointing to a spot between two genes on chromosome 5, called CDH9 and CDH10. Both genes encode cadherins – cell surface proteins that enable cells to adhere to each other. The researchers also found that a group of about 30 genes that encode cell adhesion proteins (including cadherins and neurexins) were more strongly associated with ASD than all other genes in their data set. In the developing brain, cell adhesion proteins enable neurons to migrate to the correct places and to connect with other neurons.

In a second study, Dr. Pericak-Vance completed an independent search for small genetic variants associated with ASD, in collaboration with Jonathan Haines, Ph.D., of Vanderbilt University Medical Center in Nashville. Published in the Annals of Human Genetics, the study provides a striking confirmation that ASD is associated with variation near CDH9 and CDH10.

"We are starting to see genetic pathways in ASD that make sense," says Dr. Pericak-Vance.

Finally, in a third study, reported in Nature, Drs. Hakonarson and Schellenberg led a search for genes that were duplicated or deleted in individuals with ASD. In the rare cases where those variations occurred, many tended to affect genes involved in cell adhesion. Others tended to affect genes involved in the ubiquitin-proteasome system, a cellular waste disposal system that probably affects the turnover of adhesion proteins at the cell surface.

Previous, smaller genetic studies reported a connection between male-only autism and CNTNAP2, a type of neurexin. Together, the three new studies suggest that genetic differences in cell-to-cell adhesion could influence susceptibility to ASD on a large scale. Dr. Hakonarson and his colleagues are planning an even more extensive genome-wide association study to gain a more complete picture of the genes and gene interactions involved in ASD.

The mission of NIMH (www.nimh.nih.gov) is to reduce the burden of mental and behavioral disorders through research on mind, brain and behavior. NINDS (www.ninds.nih.gov) is the nation's primary supporter of biomedical research on the brain and nervous system. NICHD (www.nichd.nih.gov) sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. NIDCD (www.nidcd.nih.gov) supports and conducts research and research training on the normal and disordered processes of hearing, balance, smell, taste, voice, speech and language and provides health information, based upon scientific discovery, to the public. NCRR (www.ncrr.nih.gov) provides laboratory scientists and clinical researchers with the resources and training they need to understand, detect, treat and prevent a wide range of diseases. NCRR supports all aspects of translational and clinical research, connecting researchers, patients and communities across the nation.

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 www.nih.gov.

For more information about autism, visit http://www.ninds.nih.gov/disorders/autism/detail_autism.htm or http://www.nimh.nih.gov/health/topics/autism-spectrum-disorders-pervasive-developmental-disorders/index.shtml.

References:
Wang K et al. "Common Genetic Variants on 5p14.1 Associate with Autism Spectrum Disorder." Nature, published online May 3, 2009.

Glessner JT et al. "Autism Genome-Wide Copy Number Variation Reveals Ubiquitin and Neuronal Genes." Nature, published online May 3, 2009.

Ma D et al. "A Genome-Wide Association Study of Autism Reveals a Common Novel Risk Locus at 5p14.1." Annals of Human Genetics, published online May 3, 2009.

Daniel Stimson | EurekAlert!
Further information:
http://www.ninds.nih.gov
http://www.nih.gov

More articles from Studies and Analyses:

nachricht Multi-year study finds 'hotspots' of ammonia over world's major agricultural areas
17.03.2017 | University of Maryland

nachricht Diabetes Drug May Improve Bone Fat-induced Defects of Fracture Healing
17.03.2017 | Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke

All articles from Studies and Analyses >>>

The most recent press releases about innovation >>>

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

Im Focus: Giant Magnetic Fields in the Universe

Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.

The results will be published on March 22 in the journal „Astronomy & Astrophysics“.

Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...

Im Focus: Tracing down linear ubiquitination

Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.

Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...

Im Focus: Perovskite edges can be tuned for optoelectronic performance

Layered 2D material improves efficiency for solar cells and LEDs

In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...

Im Focus: Polymer-coated silicon nanosheets as alternative to graphene: A perfect team for nanoelectronics

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.

Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...

Im Focus: Researchers Imitate Molecular Crowding in Cells

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.

Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

International Land Use Symposium ILUS 2017: Call for Abstracts and Registration open

20.03.2017 | Event News

CONNECT 2017: International congress on connective tissue

14.03.2017 | Event News

ICTM Conference: Turbine Construction between Big Data and Additive Manufacturing

07.03.2017 | Event News

 
Latest News

Argon is not the 'dope' for metallic hydrogen

24.03.2017 | Materials Sciences

Astronomers find unexpected, dust-obscured star formation in distant galaxy

24.03.2017 | Physics and Astronomy

Gravitational wave kicks monster black hole out of galactic core

24.03.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>