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Autism Genes Discovered; Help Shape Connections Among Brain Cells
Date:4/28/2009

the population -- attributed risk of the variant."

Hakonarson's team first performed genome-wide association studies on DNA from over 3,100 subjects from 780 families of children affected with ASDs, then performed further studies in a cohort of 1,200 affected subjects and 6,500 unaffected controls. They then replicated their results in two additional independent cohorts. In total, they analyzed DNA from 12,834 subjects.

"Autism Speaks is pleased to have facilitated this critical research, having provided both funding and access to thousands of DNA samples through Autism Speaks' Autism Genome Research Exchange (AGRE)," said Geraldine Dawson, Ph.D., Chief Science Officer for Autism Speaks. "Access to biomaterials and clinical data from thousands of families through the AGRE substantially expedites the research our community seeks and needs. Our goal is to accelerate genetic research that can ultimately lead to improved detection and medical treatments." Dawson also is a co-author of both studies in her role as a faculty member of the University of Washington.

Hakonarson's second study in Nature, also using genome-wide association tools, identified copy number variations -- deletions or duplications of DNA -- that increase a child's risk of having an ASD. Interestingly, these variants were enriched in genes that belong to two biological pathways, one including the same neuronal cell-adhesion molecule gene family that harbored the common variant reported in Hakonarson's first study. The other gene cluster impacted by copy number variations belongs to the ubiquitin degradation pathway. Ubiquitins are a class of enzymes that eliminate connections among nerve cells, and are involved with processing and degrading neuronal cell-adhesion molecules --

thus linking the two gene pathways together.

"The copy number variations we discovered are active on two gene networks that play crit
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SOURCE The Children's Hospital of Philadelphia
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