Brain Operates on 84 Percent of Human Genes, Map Shows

About 84 percent of human genes are active in the brain, a finding that may help explain its complexities and diseases, according to the most extensive DNA analysis of the organ to date.

In mapping the ways the genes link to the brain’s structures, researchers at the Allen Institute for Brain Science, funded by Microsoft Corp. co-founder Paul Allen, found that the vast majority of the 20,000 genes in the human genome play a role in the organ’s function and architecture. That’s more than in any other organ in the body, according to the report published today in the journal Nature.

Figuring out how the brain is built and organized may help scientists studying diseases, by pointing out which part of the organ uses a gene that previous research has shown to be faulty, said Seth Grant, a professor at Edinburgh University and a study author. The data outlines 400 to 500 distinct brain areas in each hemisphere.

“The human brain is the most complex structure known to mankind,” Grant said in a telephone interview. “This allows us for the first time to overlay the human genome on the human brain.”

Two brains from male donors ages 24 and 39 were mapped, and the genes’ expression between the two were very similar. Before today it wasn’t clear how alike any two brains would be. These two organs were of similar age, gender, and ethnicity. Their high degree of similarity suggests a “strong underlying common blueprint” for all human brains, the scientists wrote.

Ambitious Project

The group analyzed tissue from about 900 sites of the brains as well as a half of a third specimen and used more than 60,000 gene expression probes to establish the information, according to the report.

“It’s breathtaking in its ambition,” said Steve McCarroll, the director of genetics for the Stanley Center for Psychiatric Research at the Broad Institute in Cambridge, Massachusetts. He wasn’t involved in the study. “I was amazed to see how many anatomically defined sites they’d actually dissected out of each brain. In the effort to make a geographic atlas of regional gene expression it goes really far beyond anything that’s been done before.”

Scientists have begun to identify a number of genes with clear relevance to mental illness, McCarroll said. However, most researchers aren’t sure what these genes do in the body, and having the atlas may help for future steps, he said. For instance, if a gene is identified as a schizophrenia risk factor, knowing where it’s expressed in the brain may help explain why patients behave the way they do.

Brain Differences

There will probably be differences between male and female brains, said Ed Lein, a co-investigator at the Allen Institute, and one of the study authors. The group started with male brains because there were more of them available, he said. Previous work the Institute has done in rodents suggests there would be differences.

The Institute’s previous gene atlas of a mouse brain, when compared to today’s human blueprint, may help drug companies develop better psychiatric medicines, Lein said. Since many treatments work well in mouse models and fail in human trials, knowing how the two systems differ on a fine-grained level may help pharmaceutical companies avoid expensive failures in the future, Lein said.

Paul Allen and his sister Jody Allen Patton founded the Seattle-based institute to undertake neuroscience research. Paul Allen has committed $500 million to the institute as of 2012, according to its website.

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