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From:
Meir Weiss <[log in to unmask]>
Reply To:
Cerebral Palsy List <[log in to unmask]>
Date:
Wed, 24 Aug 2011 14:59:19 -0400
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-----Original Message-----
From: NIH news releases and news items [mailto:[log in to unmask]] On
Behalf Of NIH OLIB (NIH/OD)
Sent: August 24, 2011 14:42
To: [log in to unmask]
Subject: RESEARCHERS PRODUCE DETAILED MAP OF GENE ACTIVITY IN MOUSE BRAIN

U.S. Department of Health and Human Services 
NATIONAL INSTITUTES OF HEALTH NIH News 
National Human Genome Research Institute (NHGRI) <http://www.nhgri.nih.gov/>
Embargoed for Release:  Wednesday, August 24, 2011, 12 p.m. EDT

CONTACT: Raymond MacDougall, NHGRI, 301-402-0911,
<e-mail:[log in to unmask]>

RESEARCHERS PRODUCE DETAILED MAP OF GENE ACTIVITY IN MOUSE BRAIN
NIH-Oxford collaboration may offer clues into human brain diseases

A new atlas of gene expression in the mouse brain provides insight into how
genes work in the outer part of the brain called the cerebral cortex. In
humans, the cerebral cortex is the largest part of the brain, and the region
responsible for memory, sensory perception and language. 

Mice and people share 90 percent of their genes so the atlas, which is based
on the study of normal mice, lays a foundation for future studies of mouse
models for human diseases and, eventually, the development of treatments.
Researchers from the National Human Genome Research Institute (NHGRI), part
of the National Institutes of Health, and from Oxford University in the
United Kingdom, published a description of the new atlas in the Aug. 25,
2011, journal Neuron. The study describes the activity of more than 11,000
genes in the six layers of brain cells that make up the cerebral cortex. 

"This study shows the power of genomic technologies for making unexpected
discoveries about the basic biology of life," said NHGRI Director Eric D.
Green, M.D., Ph.D. "The brain is our most complex organ. Until we understand
how it is built and how it functions based on our genetic blueprint, we will
be hampered in keeping the brain healthy or dealing with its terrible
diseases."  

To map gene activity in all six layers of the mouse cerebral cortex, the
research team first micro-dissected the brains of eight adult mice,
separating the layers of the cortex.  They then purified processed RNAs,
including messenger RNA, from each cortical layer. 

The cell creates messenger RNA (mRNA) when genes are switched on and the DNA
code is read out to make proteins. The presence of an mRNA indicates that a
gene is turned on, and the amount of mRNA shows the extent to which the gene
is active. 

To determine which genes were turned on and to what extent, the researchers
used a relatively new sequencing technology called RNA-seq. The technique
depends on two steps. The researchers first copy processed RNA into a form
of DNA, and then sequence the resulting DNA on a second-generation, DNA
sequencing instrument. The resulting massive data set must then be analyzed
by a cluster of computers to determine which genes have been turned on in
the brain cells and to what extent. 

The international collaborators have made the new atlas freely available at
<http://genserv.anat.ox.ac.uk/layers>. 

By determining the gene activity in each layer, researchers believe it will
be possible to connect brain anatomy, genetics and disease processes with
greater precision. The research team found that more than half of the genes
expressed in the mouse cerebral cortex showed different levels of activity
in different layers. These differences point to the areas where specific
genes play important roles. 

"We found that genes associated with some human diseases were more active in
certain layers. For example, we detected genes previously associated with
Parkinson's disease in layer five and Alzheimer's disease in layers two and
three. These are correlations, not necessarily causal, but they do suggest
directions for future research," said T. Grant Belgard, lead author of the
paper and an NIH-Oxford fellow in NHGRI's Genome Technology Branch.
"Knowing the detailed pattern of expression of all genes in the cortex and
how this fits into the overall brain architecture will help us understand
how genes act together to sustain the cells and circuits that underlie
behavior and disease." 

Using the technique, researchers detected a vast array of noncoding RNAs.
These are RNAs produced from DNA that do not encode proteins, but probably
play a critical role in regulating genes and controlling biological
processes.  Some of these were active in specific layers, and many had not
previously been discovered.

The study also further demonstrated the importance of alternative splicing
in gene function within the brain.  Messenger RNA includes segments called
exons that can be stitched together in different ways to produce a mature
message that the cell uses to produce proteins.  The alternative splicing
process allows a single gene to produce many different proteins that can
have different functions in different cells or at different times in a
cell's life. 

Many alternatively spliced genes showed different distributions of the
alternative forms between layers. This includes the Mtap4 gene, whose
activity is altered in Alzheimer's disease.

Next year, Belgard and others will be involved in an effort to replicate the
mouse brain atlas for parts of the human brain. 

The research was funded in the United States by the NHGRI, and in Britain by
the Medical Research Council, Wellcome Trust, the Biotechnology and
Biological Sciences Research Council and the Marshall Scholarships. 

Oxford University's Medical Sciences Division is recognized internationally
for its outstanding research and teaching, attracting the brightest minds
from all over the world.

It is one of the largest biomedical research centres in Europe, with over
2,500 people involved in research and more than 2,800 students, and brings
in around two-thirds of Oxford University's external research income. Listed
by itself, that would make it the fifth largest university in the U.K. in
terms of research grants and contracts.

NHGRI is one of the 27 institutes and centers at the NIH, an agency of the
Department of Health and Human Services. The NHGRI Division of Intramural
Research develops and implements technology to understand, diagnose and
treat genomic and genetic diseases. Additional information about NHGRI can
be found at its website, <www.genome.gov>. 

About the National Institutes of Health (NIH): NIH, the nation's medical
research agency, includes 27 Institutes and Centers and is a component of
the U.S. Department of Health and Human Services. NIH is the primary federal
agency conducting and supporting basic, clinical, and translational medical
research, and is investigating the causes, treatments, and cures for both
common and rare diseases. For more information about NIH and its programs,
visit <www.nih.gov>.
  
##

This NIH News Release is available online at:
<http://www.nih.gov/news/health/aug2011/nhgri-24.htm>.

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<https://list.nih.gov/cgi-bin/wa.exe?A0=nihpress>.

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