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Fine-scale analysis illuminates human brain’s composition

By R&D Editors | April 16, 2012

Scientists
at the Allen Institute for Brain Science have identified similarities
and differences among regions of the human brain, among the brains of
human individuals, and between humans and mice by analyzing the
expression of approximately 1,000 genes in the brain. The study,
published online today in the journal Cell,
sheds light on the human brain in general and also serves as an
introduction to what the associated publicly available dataset can offer
the scientific community.

   

This
study reveals a high degree of similarity among human individuals. Only
5% of the nearly 1,000 genes surveyed in three particular regions show
differences in expression between humans. In addition, comparison of
this dataset to data in the Allen Mouse Brain Atlas indicates great
consistency between humans and mice, as the human visual cortex appears
to share 79% of its gene expression with that of the mouse.

   

The
dataset, which is publicly available online via the Allen Brain Atlas
data portal as part of the Allen Human Brain Atlas, holds promise for
spurring further discoveries across the research community.
Specifically, it contains detailed, cellular-level in situ hybridization
gene expression data for about 1,000 genes, selected for their
involvement in disease or neural function, in two distinct cortical
areas of several disease-free adult human brains, both male and female.

   

Genes
analyzed in this study fall into three categories: genes that serve as
indicators of cell types found in the cortex, genes that are related to
particular neural functions or diseases of the central nervous system,
and genes that hold value for understanding the neural evolution of
different species.

   

Human brain

The
analysis published today reveals high consistency of gene expression
among different regions of the human cortex—the outer rind of the
mammalian brain responsible for sophisticated information
processing—specifically the temporal and visual cortices. The vast
majority of genes expressed in these areas, 84%, demonstrate consistent
expression patterns between cortical areas. This finding supports the
hypothesis that there are common principles of organization and function
that apply throughout the cortex, and therefore studying one area in
great detail—the visual cortex, for example—may hold promise for
uncovering fundamentals about how the whole brain works. The study also
illustrates widespread conservation of gene expression among human
individuals. The study reports that of the genes analyzed, only 46 (5%)
showed variation in expression among individual, disease-free human
brains in the cortical areas examined.

   

Distinctions among species

Several
findings in the study point to differences and similarities between
humans and mice. As the mouse is the most common model for the study of
human brain function and diseases, it is crucial to understand how well
it represents the human system and where its accuracy may be limited.
Overall, the results of this study indicate good conservation of gene
expression between the two species. While the majority of gene
expression is similar, the authors of the study report some striking
differences.

   

The
findings reveal distinct molecular markers specific to each species.
Tracing those genes attributable to particular cell types—the building
blocks of brain circuits—the study authors point to a unique molecular
signature for each cortical cell type. These molecular signatures may
reflect and contribute to species-specific functions.

   

According
to the study, only 21% of gene expression in the visual cortex
exhibited differences between human and mouse, but the nature of those
differences may reveal more about what makes us uniquely human. While
very little variation among genes in the disease and evolution
categories was observed, substantial variation was reported among genes
in the cell types category, with a marked number of those genes known to
be involved in cell-to-cell communication. These data suggest that
intercellular communication may be a key link to unique brain function
in humans.

   

Advancing the field

To
date, other studies examining human gene expression have employed
either a segmented region of the brain or a select set of genes without
specific anatomic information. This human brain dataset as well as the
Allen Mouse Brain Atlas and the hundreds of studies published using its
data demonstrate that adding high-resolution, cellular-level spatial
information to gene expression profiling studies allows scientists to
learn a great deal more about how genes contribute to cell types, neural
circuits, and ultimately brain function.

   

The
study published today offers a deep introduction to the kinds of
information that can be mined from this dataset and the types of
hypotheses that it can be used to test. The entire body of data is
incorporated into the Allen Human Brain Atlas and is freely available
via the Allen Brain Atlas data portal at www.brain-map.org.

        

Large-Scale Cellular-Resolution Gene Profiling in Human Neocortex Reveals Species-Specific Molecular Signatures

Source: Allen Institute for Brain Science

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