Yale researchers map 18,000 genes

A Yale project has created the world’s largest online database for brain genes.

A team of researchers from the School of Medicine lab of associate professor of neurobiology Nenad Sestan ’99 developed an extensive database of genes in a human brain. The results, published in the Oct. 26 issue of Nature, categorize the locations and modes and degrees of expression of 18,000 genes in 16 regions of the human brain at different stages of brain development.

“This is one of the most extensive collections of genes of the brain,” postdoctoral associate Feng Cheng said.

In order to create the database, researchers examined more than a thousand brain samples in 16 brain regions including the cerebellar cortex, the neocortex, the thalamus and the hippocampus. The samples came from 57 normal human cadavers ranging from prenatal to 82 years old, and included males and females of different races. For each of the 18,000 genes examined, the team obtained information about its specific location and expression, or effect, as well as the age of the specimen, Cheng said. A database developed by postdoctoral associate Mingfeng Li provides the information for other scientists to use, Li said.

The project, which took about four years to complete, was inspired by researchers’ need to have comprehensive data on brain genes, said Yuka Kawasawa, a research scientist at Yale. Kawasawa had published a short paper on the genetic mapping of some brain regions, as had researchers at other universities, she said, but they lacked an extensive collection of more brain regions.

The project sought to remedy that lack, Kawasawa said with the online database. A week after the publication of the study, more than 30 countries had already accessed the website, Medical School associate research scientist Xuming Xu said.

In addition to mapping the genes, researchers found new trends in genetic development at different stages. Cheng said their results show that the brain displays much variation in genetic expression before birth, but this variation diminishes with age.

They also found that females and males differ in expression and location of their brain genes — even those not located on the X and Y chromosomes, Cheng said. However, he added, genetic variations are greater between different ages than between different sexes and races.

Cheng attributed the success of the research to the availability of efficient tools for gene mapping. The team used Affymetrix exon array, a popular gene mapping technique that is fast and reliable, he said. Besides the greater availability of techniques, Kawasawa added that their success stemmed greatly from Sestan’s ability to obtain the hard-to-find cadavers.

“Brain samples are hard to collect, and even harder for healthy brains,” Kawasawa said. “But [Sestan] has good contacts on clinical sides to collect brain donors, and he’s a good brain surgeon too.”

Kawasawa said that Sestan wanted to make sure that the brains remained in perfect condition, so he personally obtained them from around the country instead of having them shipped, as is customary.

Now that they have a comprehensive genetic database, the team plans to examine more carefully each of the genes as a future project, Cheng said.

The research was funded by National Institutes of Health.

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