Scientists at the Seattle-based Allen Institute for Brain Science—backed by Microsoft MSFT +1.57% co-founder Paul Allen—have spent more than a decade building an intricate map of the human brain. Today they announced the latest major discoveries from that effort, and even they were surprised by what they found. Despite the complex structure of the brain and the 20,000 genes in the human genome, brain activity is not all that diverse. Yes it’s true, no matter how much you gripe about how different you are from, say, your annoying boss, your brains really work quite similarly.
Using data from the Allen Human Brain Atlas, the scientists investigated gene “expression,” or usage, across different regions of six human brains. Because of the diversity of the genome and the brain’s intricate architecture, they thought they would find hundreds of thousands of gene-expression patterns, but they found just 32. “This was rather surprising. The number of combinatorial possibilities for these genes should be enormous,” says Michael Hawrylycz, an investigator at the institute. “But what we find is that these patterns are very stereotyped, in the sense that almost all genes look like one of these 32.”
This image from the Allen Brain Explorer shows gene expression across the human brain (Courtesy of the Allen Institute for Brain Science)
The finding, published in Nature Neuroscience, could be most useful for unlocking the mysteries behind some of the world’s most vexing brain diseases. That’s because in addition to scrutinizing the human brain, the Allen Institute scientists compared their observations to gene-expression activity in the mouse—the most commonly used animal model for developing new drugs. They found that some of the 32 gene-expression patterns were similar in mice and people, but not all of them, which could help drug researchers predict when mouse models of brain diseases are likely to be useful, and when they’re not.
Specifically, they discovered that the gene activities associated with neurons—the signal-conducting cells that make our brains work—were similar between mouse and human. But gene patterns associated with glial cells, which surround and protect neurons, were not. Glial cells have been shown to play a role in several neurological diseases, including epilepsy, autism and chronic pain. “For many of these patterns, there are genes that are just fundamentally different in how they’re used between humans and mice,” says Ed Lein, an investigator at the institute. “This is really important to know if you’re wanting to use a mouse as a model for some disease, or you’re trying understand what elements might be actually more specific to humans.”
In their paper about the research, which was conducted in partnership with Cincinnati Children’s Hospital and Medical Center and Washington University in St. Louis, Lein and his colleagues describe the relationship between “differential stability”—or patterns related to the tendency for genes to be used similarly across brain structures—and 25 common brain disorders. They found that the most highly stable genes pointed to some drug targets that are already known in diseases like autism and Alzheimer’s. But they also offer some insights that might help identify new therapeutic opportunities.
The Allen Institute for Brain Science, launched by Microsoft co-founder Paul Allen, has discovered that gene activity in the brain is not as diverse as one might think (Photo by Frazer Harrison/Getty Images).
The Allen Institute for Brain Science, which was founded in 2003 and backed by $500 million from the Microsoft veteran, is on a mission to map the human brain, and to offer its discoveries free-of-charge to the public. Its goal is to accelerate the pace of research into common brain diseases. In May, the institute launched the Allen Cell Types Database, which includes information on about 240 neurons found in mouse brains, including details about the electrical activity of neurons, as well as their shape and location. The group also updated its Ivy Glioblastoma Atlas Project, which offers genetic information about that form of brain cancer.
Allen, whose mother batted Alzheimer’s, is particularly interested in speeding up the development of new therapies against the disease. In July, the Paul G. Allen Family Foundation awarded $7 million in grants to five research teams that are working on new ways of attacking the disease.
As for the Human Brain Atlas, Allen’s scientists hope they will continue to build on the insight they’ve gained—and that the entire community of brain researchers will benefit. “We’re building a large gene network that could open up a set of candidate targets for disease,” Lein says. “It’s a much broader picture of a whole genetic network that may be associated with disease. We believe identification of gene patterns will help a lot of people to think beyond the data that they have and get access to a whole lot more information.”
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