A brainy gene

Gregory Nemec

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Mutations of a single tiny gene can derail the development of the most advanced part of the human brain, according to research by a team of scientists that includes Murat Gunel ’94Grd, a genetics and neurobiology professor at Yale.

The cerebral cortex, the “gray matter” that covers the human brain in a sort of crumpled blanket, is responsible for thought, perception, and memory—those functions that make us most human. The gene that can switch off its development is called centrosomal NDE1. Researchers discovered it by analyzing the DNA of children with microcephaly, an often-fatal disease that causes babies to develop malformed brains just 10 percent the normal size. The children’s brains can also be smooth, lacking the crevices of a normal cerebral cortex. Children with microcephaly sometimes have severe mental retardation, in addition to other neurological problems.

That mutations in NDE1 can cause the downfall of such an important part of the brain suggests, says Gunel, that the gene played a central role in brain evolution. That’s especially true for humans. A previous study showed that mouse brains were also altered by mutations in NDE1, but not as much; affected mice had brains 33 percent the normal size.

As they explain in the American Journal of Human Genetics,the researchers sequenced every single gene in the children’s DNA to find the one causing the abnormality. For the children in the study, Gunel says, the disorder was the result of inbreeding; their parents, who were related to each other, shared copies of the mutation.

Gunel hopes the discovery of NDE1 will lead to prenatal diagnosis of microcephaly—and maybe prevention, since parents could be screened for the mutation before conceiving. “These are rare diseases,” he says. “We want them to remain rare.”