Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Combining two genome analysis approaches supports immune system contribution to autism

07.12.2012
Researchers using novel approaches and methodologies of identifying genes that contribute to the development of autism have found evidence that disturbances in several immune-system-related pathways contribute to development of autism spectrum disorders.

The report published December 4 in the open-access journal PLOS ONE powerfully supports a role for the immune function in autism by integrating analysis of autism-associated DNA sequence variations with that of markers identified in studies of families affected by autism.

"Others have talked about immune function contributions to autism, but in our study immune involvement has been identified through a completely nonbiased approach," says Vishal Saxena, PhD, of the Massachusetts General Hospital (MGH) Department of Neurology, first, corresponding and co-senior author of the PLOS ONE paper. "We let the data tell us what was most important; and most tellingly, viral infection pathways were most important in this immune-related mechanism behind autism."

Genetic studies of families including individuals with autism have indentified linkages with different locations in the genome. Since traditional interpretation methods implicate the gene closest to a marker site as the cause of a condition, those studies appeared to point to different genes affecting different families. However, Saxena's team realized that, since autism has typical symptoms and affects the same biological processes, a common molecular physiology must be affecting the different families studied. To search for genetic pathways incorporating these autism-associated sites, they developed a methodology called Linkage-ordered Gene Sets (LoGS) that analyzes all of the genes within a particular distance from marker sites and ranks them according to their distance from the marker.

Saxena's team first analyzed previously identified copy-number variants (CNVs) – deletions or duplications of large DNA segments – linked to autism, and identified associated pathways for the first time. After finding that the two pathways most frequently affected by CNVs in autism were related to immune function, they went on to identify three additional immune-related pathways among the top 20 sets of genes with autism-associated CNVs.

They then conducted LoGS analysis on the five CNV-identified pathways, which they called iCNV-5, along with 186 other pathways involved in a range of biologic functions, ranking them according to their distance from marker sites identified in family studies. Four of the five iCNV-5 pathways received the top four rankings in the LoGS analysis, strongly supporting an immune function role in autism. Additional pathways involved in neurodevelopment were highly ranked in both the CNV and LoGS analyses.

"The idea behind LoGS is akin to viewing a digital photograph," says Saxena, an instructor in Neurology at Harvard Medical School. "When one looks at a digital image from very close up, one only sees a few pixels and is unable to recognize the picture. Zooming out however, makes the picture understandable. In the same way, looking at single genes may lead to a disorganized view of a disease, but zooming out to the pathway level clarifies and unifies the mechanism."

The immune system genes included in the iCNV-5 pathways code for two different types of proteins – interferons, in which DNA segments were reduced or absent in the iCNV-5 pathways, and chemokines, which showed duplication of DNA segments. Interferons help control viral infections, so reduced production of interferons could delay control of a viral infection in a pregnant woman and her fetus. Viral infections also induce the production of chemokines, which have an additional role in fetal brain development. A combination of reduced interferon levels, which would prolong the course of a viral infection, and elevated chemokine levels could potentially alter brain development in an infected fetus. The researchers are continuing to investigate how these and other immune pathways may be involved in the development of autism.

The co-senior author of the PLOS ONE report is Isaac Kohane, MD, PhD, Boston Children's Hospital. Additional co-authors are Shweta Ramdas, University of Michigan; Courtney Rothrock Ochoa, University of South Alabama College of Medicine; David Wallace, PhD, Massachusetts Institute of Technology; and Pradeep Bhide, PhD, Florida State University. The study was supported by National Institutes of Health grant P50MH94267 and the Nancy Lurie Marks Foundation.

Massachusetts General Hospital, founded in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of more than $750 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, reproductive biology, systems biology, transplantation biology and photomedicine. In July 2012, MGH moved into the number one spot on the 2012-13 U.S. News & World Report list of "America's Best Hospitals."

Sue McGreevey | EurekAlert!
Further information:
http://www.massgeneral.org/

More articles from Life Sciences:

nachricht Fingerprint' technique spots frog populations at risk from pollution
27.03.2017 | Lancaster University

nachricht Parallel computation provides deeper insight into brain function
27.03.2017 | Okinawa Institute of Science and Technology (OIST) Graduate University

All articles from Life Sciences >>>

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

Northern oceans pumped CO2 into the atmosphere

27.03.2017 | Earth Sciences

Fingerprint' technique spots frog populations at risk from pollution

27.03.2017 | Life Sciences

Big data approach to predict protein structure

27.03.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>