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Genome-wide atlas of gene enhancers in the brain online
Date:1/31/2013

mutations to actual biological functions," Visel says.

As an example of how the enhancer atlas could be used in this manner, Visel says that if through genetic studies a certain region of the human genome has been linked to a specific neurological disorder but that region does not contain any protein-coding genes, checking the atlas could reveal whether the region is home to any distant-acting gene enhancers.

"If there is a gene enhancer in the region," Visel says, "researchers could determine exactly how the enhancer or a mutated form is related to the disorder. This encompasses a lot of territory in the human genome. More than half of all the disease-related DNA sequence changes discovered in genome-wide screens to date fall within the 98-percent of human genome sequences that do not code for proteins. These 'non-coding' sequences were once dismissed by many as 'junk DNA' but are now known to harbor critical gene regulatory functions."

Visel says the enhancer atlas also provides a "molecular toolbox" that can be used to re-locate the expression of certain genes to specific regions of the brain in experimental applications. This could help researchers gain new insights into how the brain develops and how the human brain has evolved.

"The evolution of the gene regulatory architecture may have been one of the drivers of the extremely advanced brains that we see in primates in general and humans in particular," he says.

While continuing to map and annotate additional enhancers, Visel and his colleagues are now also studying the biological mechanisms related to some of these enhancers in more detail.

"We still only partially understand how gene enhancers work in the context of a living brain, i.e., what proteins bind to them, how mutations change their function, and what exactly the role of these sequences is in the context of human neurological disorders," Visel says. "Clearly, there is more work to do."

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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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