Fine-scale analysis of the human brain yields insight into its distinctive composition

April 12, 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 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 Atlas indicates great consistency between humans and mice, as the human visual cortex appears to share 79% of its with that of the mouse.

The dataset, which is publicly available online via the Allen Brain Atlas data portal as part of the Allen , holds promise for spurring further discoveries across the research community. Specifically, it contains detailed, cellular-level in situ hybridization for about 1,000 genes, selected for their involvement in disease or , 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 , 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 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 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 and the types of hypotheses that it can be used to test. The entire body of data is incorporated into the Allen Atlas and is freely available via the Allen data portal at www.brain-map.org.

Explore further: Allen Institute for Brain Science announces first comprehensive gene map of the human brain

More information: Zeng et al., Large-Scale Cellular-Resolution Gene Profiling in Human Neocortex Reveals Species-Specific Molecular Signatures. Cell (2012) doi: 10.1016/j.cell.2012.02.052

Related Stories

Allen Institute for Brain Science announces first comprehensive gene map of the human brain

April 12, 2011
The Allen Institute for Brain Science has released the world's first anatomically and genomically comprehensive human brain map, a previously unthinkable feat made possible through leading-edge technology and more than four ...

Novel analysis sheds new light on the mechanisms of brain development

August 1, 2011
Scientists at the Allen Institute for Brain Science have taken an important step in identifying how the brain organizes itself during development. The findings, published in the Journal of Comparative Neurology today, describe ...

Allen Institute for Brain Science launches new atlas, adds new data and tools to others

November 14, 2011
The Allen Institute for Brain Science announced today the launch of a new brain atlas resource and updates to four existing resources, all publicly available online to accelerate brain research around the globe. The new atlas, ...

Researchers produce detailed map of gene activity in mouse brain

August 24, 2011
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 ...

Recommended for you

The 16 genetic markers that can cut a life story short

July 27, 2017
The answer to how long each of us will live is partly encoded in our genome. Researchers have identified 16 genetic markers associated with a decreased lifespan, including 14 new to science. This is the largest set of markers ...

A rogue gene is causing seizures in babies—here's how scientists wants to stop it

July 26, 2017
Two rare diseases caused by a malfunctioning gene that triggers seizures or involuntary movements in children as early as a few days old have left scientists searching for answers and better treatment options.

Scientists provide insight into genetic basis of neuropsychiatric disorders

July 21, 2017
A study by scientists at the Children's Medical Center Research Institute at UT Southwestern (CRI) is providing insight into the genetic basis of neuropsychiatric disorders. In this research, the first mouse model of a mutation ...

Scientists identify new way cells turn off genes

July 19, 2017
Cells have more than one trick up their sleeve for controlling certain genes that regulate fetal growth and development.

South Asian genomes could be boon for disease research, scientists say

July 18, 2017
The Indian subcontinent's massive population is nearing 1.5 billion according to recent accounts. But that population is far from monolithic; it's made up of nearly 5,000 well-defined sub-groups, making the region one of ...

Mutant yeast reveals details of the aberrant genomic machinery of children's high-grade gliomas

July 18, 2017
St. Jude Children's Research Hospital biologists have used engineered yeast cells to discover how a mutation that is frequently found in pediatric brain tumor high-grade glioma triggers a cascade of genomic malfunctions.

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.