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Gene activity in the brain depends on genetic background
Date:10/19/2010

SEATTLE, Wash.October 18, 2010Researchers at the Allen Institute for Brain Science have found that the same genes have different activity patterns in the brain in individuals with different genetic backgrounds. These findings may help to explain individual differences in the effectiveness and side-effect profiles of therapeutic drugs and thus have implications for personalized medicine. The study is available in this week's online early edition of the Proceedings of the National Academy of Sciences (www.pnas.org).

In this study, the authors compared where in the brain each of 49 different pharmaceutically related genes is expressed, or turned on, in seven genetically distinct groups of mice with known genealogical relationships. By analyzing 203 distinct brain areas over 15,000 thin sections of tissue, they precisely mapped where these genes are active, down to the level of individual cells. The genes all encode molecular targets of well-known pharmaceuticals, such as antidepressants, antipsychotics and pain relievers including Prozac, Imitrex, and Aricept.

More than half of the genes examined showed striking, localized differences in expression patterns between the different genetic groups, or strains, of mice. For example, the dopamine D2 receptor genewhich encodes a target of action of Zyprexa, a drug used for schizophrenia and bipolar disorderis active in a memory-related area called the entorhinal cortex in one strain of mice, but not in two others. Because different parts of the brain have different functions, variations in the localization of gene activity likely have functional implications.

"It is clear that to understand how genes translate to behavioral and other differences between individuals and species, we need to look beyond just the inherited sequences of the genes themselves," said Allan Jones, chief executive officer of the Allen Institute for Brain Science. "Our results sho
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Contact: Aaron Blank
aaronblank@feareygroup.com
206-343-1543
Allen Institute for Brain Science
Source:Eurekalert

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