A private research group based in Seattle, Wash. has just announced the results of one of the largest systematic efforts in biology since the sequencing of the human genome.
Writing in the Jan. 10issue of Nature, scientists from the Allen Institute for Brain Science describe a new public database of gene expression in the mouse brain. The effort was sponsored by Microsoft co-founder Paul Allen.
The database represents the culmination of years of effort and offers a major new resource for neuroscientists. Invaluable volumes of data have been collected and made easily accessible through the Internet.
There are over 20,000 distinct genes in the mouse genome, but not all of these genes are expressed in every cell. Only a small subset of genes is active in any given cell at any stage of mouse development.
An expressed gene is one that is being used by a cell to produce proteins. Understanding when and where each gene is expressed in the brain will help neuroscientists understand how the brain develops, functions and becomes diseased.
Any neuroscientist can take a mouse brain, slice it into thin sections and use specific markers to locate where a particular gene is active. The Allen Institute's major advancement was to industrialize this process, automatically sectioning, staining and imaging mouse brains at the rate of 16,000 sections per week.
The stains used a technique known as in situ hybridization. A complementary strand of RNA was produced to recognize and bind to a small length of each transcribed gene. This probe was labeled with a fluorescent marker so it would be visible.
Images of the thin sections were then reconstructed into three-dimensional atlases, one for each gene. To correct for small variations in the shape of mouse brains, computer processing altered all of the atlases to ensure they conformed to the dimensions of a single "model" brain.
Around 85 million images were produced in total, representing over 600 terabytes of information. By comparison, it is estimated that the entire contents of the Library of Congress are approximately 10 terabytes.
Understanding how the nervous system operates by discovering the "instructions" that code for certain traits will provide insight into the relationship between genes and behavior.
Neuroscientist Alex Kolodkin of the Solomon H. Snyder department of neuroscience at Hopkins said of the project, "This is an impressive achievement. The Allen Institute is to be commended for designing and implementing high-throughput gene expression analysis in the mouse brain.
"Though individual expression patterns of any single gene are likely to require confirmatory analysis, this work heralds a new era of gene expression analysis and should provide a foundation for undertaking more complex assessments of gene expression pattern alterations following behavioral activity or clinically relevant insults to the brain."
Mice are often used as models for studying human biology. Both the mouse brain and the mouse genome are remarkably similar to their human counterparts. Advances in understanding the mouse brain will directly translate to human advances.
The Allen Brain Atlas allows scientists to view all the locations at which any of thousands of genes are activated. Scientists can search any anatomical region of the brain for any combination of genes and see the results in a three-dimensional analysis.
The inability to fully understand the genetic foundations that give rise to the brain's structural and cellular aspects has been a major roadblock to progress for modern scientists.
The Allen Brain Atlas has made an important first step in understanding this complexity by delivering and making available the tools scientists need to proceed with their own research.
David Ginty, a Hopkins neuroscientist, commented, "With the sequencing of the genomes of model organisms and identification of the 25,000 or so genes, one major challenge is understanding gene function in cells of the nervous system and elsewhere. The ABA provides the first comprehensive overview of gene expression patterns in the brain.
"I think that this wealth of new information will help not only to define the molecular diversity in the nervous system but also to facilitate the analysis of gene function in the developing adult brain using transgenic and other approaches."
