Navigation Links
Combining two genome analysis approaches supports immune system contribution to autism
Date:12/6/2012

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.


'/>"/>

Contact: Sue McGreevey
smcgreevey@partners.org
617-724-2764
Massachusetts General Hospital
Source:Eurekalert

Related biology news :

1. Trial seeks improved lung-cancer screening by combining imaging and biomarkers
2. Study finds prioritizing rather than canvassing entire plant genome may lead to improved crops
3. UC Davis researchers aid effort to sequence the complex wheat genome
4. USDA scientists and cooperators sequence the wheat genome in breakthrough for global food security
5. Bread wheats large and complex genome is revealed
6. Genome decoded: Scientists find clues to more disease-resistant watermelons
7. Short DNA strands in the genome may be key to understanding human cognition and diseases
8. Researchers decode birch tree genome sequence for the first time
9. Pear genome provides new insight into breeding improvement and evolutionary trace analysis
10. USDA funded research leads to key discoveries in the pig genome
11. Researchers sequence swine genome, discover associations that may advance animal and human health
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/18/2017)... Inc., a global expert in SoC-based imaging and computing solutions, has ... features the company,s hybrid codec technology. A demonstration utilizing TeraFaces ® ... be showcased during the upcoming Medtec Japan at Tokyo Big Sight ... Las Vegas Convention Center April 24-27. ... Click here for an image of the ...
(Date:4/13/2017)... , April 13, 2017 UBM,s Advanced ... will feature emerging and evolving technology through ... Innovation Summits will run alongside the expo portion of ... sessions, panels and demonstrations focused on trending topics within ... advanced design and manufacturing event will take place June ...
(Date:4/11/2017)... GARDENS, Fla. , April 11, 2017 /PRNewswire/ ... management and secure authentication solutions, today announced that ... by Intelligence Advanced Research Projects Activity (IARPA) to ... IARPA,s Thor program. "Innovation has been ... and IARPA,s Thor program will allow us to ...
Breaking Biology News(10 mins):
(Date:5/19/2017)... ... May 19, 2017 , ... In response to the strong base ... Medical Systems, Inc. announces the release of their Gait Trainer 3 with an Integrated ... a biomedical system to aid in rehabilitating individuals with cerebral palsy, traumatic brain injury, ...
(Date:5/18/2017)... ... May 16, 2017 , ... Clinical Supplies Management (“CSM”), ... as the company continues to grow. CSM has doubled in size over the ... executing an aggressive growth strategy. , Roger Gasper joins CSM as Chief Financial Officer. ...
(Date:5/18/2017)... ... May 17, 2017 , ... ... process optimization firm for the life sciences and healthcare industries, is honored that ... Traceability for Medical Devices conference in Brussels, Belgium. , Crowley played a crucial ...
(Date:5/18/2017)... ... ... When James Sherley, was notified earlier this year that his company Asymmetrex had ... The Silicon Review , he was not surprised as others might be. Sherley ... recognition by Silicon Valley was particularly meaningful. Our selection by The Silicon ...
Breaking Biology Technology: