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Scientists, Supported by Microsoft Co-Founder, To Assemble Online Atlas of Brain

The New York Times -- Backed by millions of dollars in financial support from Paul G. Allen, a founder of Microsoft, a team of scientists has set out to pinpoint the roughly 20,000 genes responsible for building and operating the human brain. From there, the scientists will put together a highly detailed atlas of the mammalian brain and make it available to the public through an online database.

To accomplish that goal, they are relying heavily on the genome of the common mouse, which genetically bears remarkable similarities to humans.

“It’s almost embarrassing when you think about it,” said Dr. Mark Boguski, director of the Seattle-based Allen Institute for Brain Science, which is leading the effort. “But we share 99 percent of our genes with mice.”

Finding genes in mice that control how the brain develops and functions could help scientists find new drugs for neurological diseases and achieve a greater understanding of human behavior, say scientists involved with the project, called the Allen Brain Atlas.

The human genome contains about 30,000 genes. All but 300 of them have a functional counterpart in the mouse genome. That genetic bond will allow Boguski and his team at the Allen Institute, founded recently with a $100 million donation from Allen, to study gene expression in the mouse brain and transfer the results to humans.

“If we can understand gene expression in the brain, we can learn so much about neurological diseases and the genetic component to human behaviors, like emotion,” Allen said.

The team’s first step is to identify which genes are active in different regions of the brain -- a daunting task, since an estimated two-thirds of the mouse and human genomes play some role in brain activity.

“It’s like trying to build a coffee table from 30,000 pieces of furniture without an instruction manual,” Boguski said. “We don’t know which parts are needed, but as we build the table we will gain functional information into how the pieces work.”

When all of the pieces, or genes, are identified, the team can assemble a gene expression map of the brain. That will allow scientists to detect neural functions like emotion, memory and language, and determine how they are encoded in the genome.

If a gene with a previously unknown purpose appears active in a part of the brain responsible for mood, for example, then it becomes a target for manic depression and other mood disorders, Boguski said. Knowing which genes are expressed in the brain and the roles they play could conceivably open the door to new drug targets for an array of neurological diseases -- schizophrenia, Alzheimer’s and autism, to name a few.

Experiments that involve manipulations of the human brain often are dangerous and inappropriate, but the same projects with the genes of mice can be simple and revealing, scientists say.

The Allen Institute’s brain atlas will not be the first. A handful of others exist, but most are based on brain scans rather than on gene expression maps.

Since 1999, the National Institute of Mental Health has financed an effort to create a brain map using the mouse genome, the Brain Molecular Anatomy Project, or BMAP. But the Allen project has goals on a bigger scale, said Dr. Thomas Insel, director of the mental health institute. While the anatomy project can analyze 600 to 800 genes a year, Boguski’s team is shooting for about 10,000 genes a year.