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

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

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