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The allen institute for brain science is a 501 (c) (3) nonprofit medical research organization based in seattle, washington



GENE ACTIVITY IN THE BRAIN DEPENDS ON GENETIC BACKGROUND
New Study by the Allen Institute for Brain Science Has Implications for Individual Differences in Drug
Safety and Efficacy
SEATTLE, Wash.—October 18, 2010—Researchers 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
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 gene—which encodes a
target of action of Zyprexa, a drug used for schizophrenia and bipolar disorder—is 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 show that genetic background—the specific
blend of gene variants comprising an individual genome—can influence how the activity of a given gene is
regulated and where it is expressed.”
Taken all together, the data from the study demonstrate that closer genetic relatives exhibit fewer differences in
gene expression patterns, whereas more distant relatives show greater variation. Interestingly, the researchers
found that the expression variations between genetic strains were more likely to be found in areas of the brain
that evolved more recently. These regions are most commonly linked to higher order functions such as cognition,
social behavior, learning and memory.
“This study shows how large-scale datasets can be used to reveal fundamental biological patterns that would
likely be missed otherwise,” said Jones. “It is likely that many important differences between individuals and
species may result from combinations of many small but clear differences in gene expression.”
Jones added, “Our ongoing Allen Human Brain Atlas project, which will provide gene expression data across the
brains of multiple donors, will help researchers translate these results from an animal model to a human system.”
The data in this study are openly available to the public as the Mouse Diversity Study via the ALLEN Brain Atlas
data portal ator directly at
Citation: JA Morris et al PNAS, published
online October 18, 2010, doi: 10.1073/pnas.1003732107

About the Allen Institute for Brain Science

Launched in 2003, the Seattle-based Allen Institute for Brain Science is an independent, 501(c)(3) nonprofit
medical research organization dedicated to advancing brain research. Started with $100 million in seed money
from philanthropist Paul G. Allen, the Institute takes on projects at the leading edge of science—far-reaching
projects at the intersection of biology and technology. The resulting data create publicly available resources that
fuel discovery for countless other researchers worldwide. The Institute’s data and tools are available on the Web
at

Media Contact:
Aaron Blank, for the Allen Institute for Brain Science
(206) 343-1543, (425) 736-5456 (mobile),

Source: http://www.alleninstitute.org/Media/documents/press_releases/2010_1018_PressRelease_PNAS_MouseDiversityStudy.pdf

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