First human whole-brain genetic map created
A team at the Allen Institute for Brain Science has created the first human brain-wide map of gene expression data.
The achievement marks a major milestone for the Allen Institute, which previously had released similar data sets for the mouse brain. The data set will allow scientists to test new hypotheses about how the particular genetic codes of different brain areas lead to the unfathomably complex, unified organ.
The task of creating an atlas of human gene expression in the brain is not an easy one. First, acquiring clinically normal brains can be a drag -- brains can be among the hardest organs to get permission to excise, and to chop up for study.
Once a sample is available, the scientists need to be extremely precise with how they partition the brain so they can reliably connect genes to regions. One wrong cut and the data become imperfect.
Scientists at the Allen Institute -- which is based in Seattle and is run by Paul Allen, the co-founder of Microsoft -- acquired two brains, one from an NIH tissue bank and another from a bank at UC Irvine. The brains had belonged to men ages 24 and 39. The process included acquiring permission from the next-of-kin.
The scientists then put the brains through a complex pipeline. First, they collected high-resolution pictures of each brain in an MRI machine. Then, they chopped the brains up into smaller pieces so they could detect gene expression in 900 distinct brain regions — possible because genetic transcripts remain in the tissue after death if it is cared for properly. Finally, they combined the imaging data with the gene expression information. The result is the most accurate and thorough collection of human brain gene expression data ever produced.
The main benefit of the data set, which is publicly available, will be to the thousands of neuroscientists whose hypotheses would benefit from genetic information but who currently rely on what we know about mouse brains for that information. For example, a scientist who studies fear in humans by taking images of brain activity in an MRI machine while a subject looks at fearful images can now look to see what genes are expressed in the parts of the brain that “light up” during the study. Before, they would have had to look to a scattered literature of individual studies, or to gene data from animal models.
The Allen Institute researchers have come up with some interesting nuggets of their own hidden in the data set. For example, when they looked at the gene expression data from the cortex -- the outer shell of the brain that is generally related to higher-level thought and cognition -- they found a surprising amount of uniformity in the genes that were expressed there when compared to other areas that sit below the cortex. This suggests both that the cortex is easily expandable -- perhaps explaining its rapid evolution in primates -- and that the cortex is not complicated simply because of its genetic programming. Instead, aspects like the delicate balances of activity from different types of cells may distinguish the functions of different cortical areas.
The researchers point out that it is still way too early to say for sure, and they also note that these are only two brains (though a third half-brain was also analyzed as part of the study). While the team found striking consistency in gene expression between them, the two brains that formed the heart of the study came from men of similar background, belying the likely diversity of human genetics.
The next steps, they say, will involve collecting many more brains to see just how consistent their findings are across the human population.
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