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Gene expression in human brain
An image from the Allen Brain Explorer shows gene expression across the human brain. (Credit: Allen Institute for Brain Science)

Researchers say they’ve traced 32 of the most common genetic patterns at work in the human brain, as part of a mapping project that could lead to new insights about Alzheimer’s and other diseases.

“We’re really trying to understand the genetic basis for the architecture of the human brain,” said Ed Lein, a researcher at the Allen Institute for Brain Science and one of the authors of a study published online today by Nature Neuroscience.

Lein told GeekWire that the study, based on data from the Allen Human Brain Atlas, demonstrates “we’re really much more similar than we are dissimilar” when it comes to the genetic code for our brain’s wiring. The genes that are most consistently associated with specific regions of the brain include some associated with Alzheimer’s, Parkinson’s and Huntington’s disease, as well as epilepsy and disorders associated with cocaine and nicotine use.

Ed Lein
Ed Lein

Genetic studies are usually aimed at identifying individual differences that can be associated with diseases or other traits. But in this case, the sample size – involving six human brains – was too small to identify statistically significant differences. So Lein said he and his colleagues “turned the question on its head” to look for the most widely shared genetic commonalities.

The 32 modules described in the study were identified by determining which patterns of gene expression were most commonly found across 132 structures in the six brains. The study’s authors say most of the ways in which the human genome’s 20,000 genes come into play in the brain involve one of these 32 expression patterns.

“It’s a reasonable hypothesis that these patterns should be found in every human brain,” said Michael Hawrylycz, another Allen Institute neuroscientist who is a principal author of the study. “In fact, you would be surprised if you didn’t find them.”

The researchers wrote in the Nature Neuroscience paper that such genetic patterns could serve as “a baseline from which deviations in individuals may be measured and associated with diseases such as autism, schizophrenia, epilepsy and major depression.”

Christof Koch, the Allen Brain Institute’s president and chief scientific officer, said he was surprised to find that so few patterns could explain most of the gene variability across the human brain. “There could easily have been thousands of patterns, or none at all,” he said in a news release. “This gives us an exciting way to look further at the functional activity that underlies the uniquely human brain.”

Michael Hawrylycz
Michael Hawrylycz

To get a sense of just how uniquely human the patterns were, the scientists compared them with the patterns found in mouse brains as reflected in another database compiled by the institute, known as the Allen Mouse Brain Atlas.

The study determined that the genes associated with neurons were highly conserved between the two species. However, there were significant differences between mice and humans when it came to the genes associated with glial cells, which regulate how neurons behave. That’s consistent with a growing sense that glial cells play a crucial role in human brain function.

Such research feeds into the Obama administration’s $100 million BRAIN Initiative as well as the European Commission’s $1 billion Human Brain Project. Both efforts are aimed at understanding how the brain works, on scales ranging from the molecular, genetic and cellular levels to high-order mental processes.

“I personally can think of at least five questions that people can follow up on,” Hawrylycz told GeekWire.

In addition to Hawrylycz, Lein and Koch, the authors of “Canonical Genetic Signatures of the Adult Human Brain” include 27 researchers from the Allen Institute for Brain Science, Cincinnati Children’s Hospital and Medical Center, Washington University in St. Louis, Northeastern University, Central European University, Xi’an Jiaotong-Liverpool University, the University of Cincinnati, the University of Washington, Georgetown University, Dana-Farber Cancer Institute and Brigham and Women’s Hospital. Funding was provided by the Allen Institute and the National Institute of Drug Abuse.

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