Scientist 'Explorers' Create Gene Map of the Brain

Fran Lowry

April 18, 2011

April 18, 2011 — The Allen Institute for Brain Science, founded by Microsoft cofounder Paul Allen, has unveiled the world's first comprehensive gene map of the human brain.

The unique map will help scientists explore and research neurologic diseases and other brain disorders.

According to a press release from the Allen Institute, the world's first anatomically and genomically comprehensive human brain map is a "previously unthinkable feat made possible through leading-edge technology and more than 4 years of rigorous studies and documentation."

The institute hopes that the map will speed scientists' understanding of how the human brain works and prompt new research among neuroscientists around the world.

The map identifies 1000 anatomical sites in the human brain, backed by more than 100 million data points that indicate the particular gene expression and underlying biochemistry of each site. Clinicians can use it to explore the brain and see how disease and trauma, including physical brain injuries and mental illness, affect specific areas of the brain.

In an interview with Medscape Medical News, Allan Jones, PhD, chief executive officer of the Allen Institute for Brain Science, said that, until now, such a detailed map of the human brain has not existed.

"What is really unique about the map that we have created is that we have added on to what traditionally clinicians might look at in terms of a magnetic resonance or MR scan, for example, where they get anatomic regional delineations" he explained. "What we have done is hung on top of that scaffolding of an MR very detailed information about what genes are turned on in those areas.

"We are actually measuring the gene expression levels, the genes that are turned on, and that gives us a clue as to the underlying biochemistry of those particular regions of the brain," he added.

Speed of the Essence

The first comprehensive gene map of the human brain is made up of 2 postmortem brains that are as normal as possible.

Brain Stain

"We have to process them very quickly because the RNA that we are trying to assay starts to degrade upon death. We need to have processed the tissue to at least get it frozen very quickly, within 24 hours of the time of death," Dr. Jones said.

The institute works with medical examiners and brain banks on both the East Coast and West Coast. When a possible donor becomes available, the institute obtains consent from the family, and once that is obtained, the process of performing magnetic resonance imaging (MRI) begins.

While the brain is in the MRI machine, it undergoes diffusion tensor imaging, "which gives us a bit of the wiring of the brain," to provide a standard coordinate system. "This provides that common framework by which many clinician-scientists would actually enter data," Dr. Jones said.

Once the MRI is finished, the process of fragmenting the brain into specific atomic regions begins.

"We begin by doing 'slabbing,'" Dr. Jones said. "We slab the brain into 1-cm slabs from front to back. These are then frozen, and they are shipped to the Allen Institute in Seattle. When they get here, we take those whole slabs and start doing thin sections of them, which we stain with standard histological stains. This gives us the detailed information about the brain anatomy."

The 2 brains in the map are 94% similar. "We were very encouraged when we saw that the first 2 brains actually gave similar results," Dr. Jones noted.

Impressive Accomplishment

"Wow!" Michele Tagliati, MD, professor of neurology and director of movement disorders at Cedars-Sinai Medical Center, Los Angeles, California, commented on hearing of the new human brain map. "This is quite an amazing accomplishment. I would define it as more of a leap rather than a step forward," he told Medscape Medical News.

"This is a tremendous event and I'm very impressed," Dr. Tagliati said.

There are many ways that this new brain map will be relevant to clinical practice, he added.

"Having this genetic map will be a great help to advance our understanding of how the brain works and also how it stops working. From a purely scientific standpoint, from a clinical standpoint, and from a methodological standpoint, this reinforces the idea that you have to integrate data and information from a variety of sources if you want to have a true understanding and a true shot at managing the complex diseases of the brain."

Dr. Jones and Dr. Tagliati have disclosed no relevant financial relationships.