A comprehensive atlas of the adult human brain that reveals the
activity of genes across the entire organ has been created by
scientists.
The
map
was created from genetic analyses of about 900 specific parts of two
"clinically unremarkable" brains donated by a 24-year-old and
39-year-old man, and half a brain from a third man.
Researchers at the
Allen Institute for Brain Science
in Seattle said the atlas will serve as a baseline against which they
and others can compare the genetic activity of diseased brains, and so
shed light on factors that underlie neurological and psychiatric
conditions.
"The human brain is the most complex structure known to mankind and one of the greatest challenges in modern
biology is to understand how it is built and organised," said
Seth Grant, a professor of molecular
neuroscience at Edinburgh University who worked on the map.
"This
allows us for the first time to overlay the human genome on to the
human brain. It gives us essentially the Rosetta stone for understanding
the link between the genome and the brain, and gives us a path forward
to decoding how genetic disorders impact and produce brain disease," he
said.
The power of the brain arises from its neural wiring, its
variety of cells and structures, and ultimately where and when different
genes are switched on and off throughout the 3lb lump of flesh.
From
more than 100 million measurements on brain pieces, with some only a
few cubic millimetres, the scientists found that 84% of all genes are
turned on in some part of the organ. Gene activity in next door regions
of the cortex, the large wrinkly surface of the brain, was very similar,
but distinct from that in lower parts, such as the brain stem.
More
detailed analysis of the cortex revealed patterns in gene activity that
corresponded to regions with specific roles in the brain, such as
movement and sensory functions.
The atlas revealed no major divide
in gene activity on the left and right sides of the brain, suggesting
that expertise generally handled by one hemisphere, such as language,
comes from more subtle differences than the study could spot.
Though
both brains came from men of a similar age and ethnicity, the pattern
of gene activity was so similar that researchers suspect there may be a
common blueprint for the expression of genes in the human brain. Work is
now under way on donated tissues from both sexes to check how
consistent that genetic blueprint might be among people with healthy
brains.
Scientists have constructed similar genetic atlases for
rodents in the past, but the shortage of donated human brains, coupled
with the destructive nature of the tests, and the 1,000-fold increase in
size, meant a human equivalent was more of a challenge.
Writing in the journal
Nature,
the scientists describe how they first scanned the donated brains and
then chopped them into tiny pieces. For each lump, they measured
activity levels for all of the 20,000 or so genes in the human genome.
The atlas, which overlays the genetic results on to a 3D image of the brain, is freely available for researchers to use online.
Grant
said that future studies will look to connect the genetic brain atlas
with other genetic studies or brain scans of abnormal or diseased
brains. That could highlight genes that play a role in brain conditions
and point the way to drug treatments that dampen down or ramp up gene
activity.
Clyde Francks
at the Max Planck Institute for Psycholinguistics in the Netherlands is
already using genetic data from the Allen Institute for Brain Science
to pinpoint genes that give rise to brain asymmetries in a set of 1,300
Dutch students.
