Sunday, March 23, 2008

The Genetics of Language

Locating Language: The neural circuitry for speech and language is typically localized in the left hemisphere of the brain, along a region called the Sylvian fissure that stretches from Broca's area to Wernicke's. Researchers are searching for the genes that wire these regions and produce the uniquely human capacity for speech. Broca's area, highlighted above in green, is associated with speech and language output. Wernicke's area, highlighted in red, is associated with language comprehension.
Credit: John MacNeill

Daniel Geschwind reaches up to his office bookshelf, takes down a three-dimensional puzzle of the human brain, and begins trying to snap the plastic pieces together. A neurogeneticist at the University of California, Los Angeles, Geschwind hopes the puzzle will help him describe the parts of the brain that control speech and language. But for the life of him, he can't figure out how the left and right hemispheres attach. "I'm really bad spatially, so don't make fun of me," he pleads. "It's like I'm having a little stroke or something. I'll get it together, and then I'll figure it out."

The plastic model may have momentarily flummoxed Geschwind, but when it comes to the genes that govern the brain's development and functions, he excels at putting the pieces together. Over the past few years, he has emerged as one of the leading geneticists in a nascent field that aims to spell out which genes are related to speech and language development--and how our intelligence and communication skills evolved beyond those of our ape relatives, giving us the unique ability to speak.

Research like Geschwind's sits at the intersection of two fields: behavioral genetics and evolutionary bi­ology. Each field depends on the other to make sense of the flood of studies on the genetics of language now pouring out of labs around the world. To peer into the human brain and see how it typically stores, uses, and comprehends words, Geschwind investigates not only normal human brains but also those where the process goes awry, studying the genes of families afflicted by autism, dyslexia, schizophrenia, and other conditions that can involve speech and language disorders. This research may help make diagnosis and treatment of language-related disorders more precise, but it also has a more basic purpose. "Studying disease is really a fundamental way to understand normal function," says Geschwind. "Disease has given us extraordinary insight to understand how the brain works or might not work."

While behavioral genetics compares the genes of people with different abilities, evolutionary biology compares the genes of different species. Researchers use this data to determine what limits other species' communication skills and what expanded ours so dramatically that language became one of our defining characteristics. Geschwind's own forays into evolutionary bi­ology have led him to look at DNA in the brains of chimpanzees, monkeys, and even songbirds. "A lot of people think our lab is all over the place," he says. "It's actually pretty integrated. Language is complex, and the only way we're going to have a hit is when two or three findings point to the same place."

With the help of improved techniques for detecting DNA, as well as cutting-edge analytical tools and the genome sequences of species from humans to mice, Geschwind and other researchers have begun to tease out how we evolved the capacity for sophisticated speech. But though neuroscientists working in the postgenomic era have made a lot of progress, they have only begun to scratch the surface of how the relevant genes are collectively put into action.

FOXP2 Hunting
Despite more than a decade of effort and many tantalizing leads, neurogeneticists have so far definitively linked only a single gene to speech and language. The story of its discovery begins in 1990, when clinical geneticists at the Institute of Child Health in London first reported a speech disorder that appeared in three generations of Britons known as the KE family. The doctors took note of 15 affected members who seemed to have inherited problems with grammar, syntax, and vocabulary that were tied to poor control of facial muscles and difficulty pronouncing words. Although it seemed clear that there had to be a genetic link, researchers hunted for more than a decade before they found the gene responsible.

The big break came in 1998, when University of Oxford geneticists led by Anthony Monaco and Simon Fisher identified a distinct chunk of chromosome 7 linked to the speech and language problems found in the KE family. Yet the region held dozens of genes, and they couldn't pinpoint the one bad actor. Enter Jane Hurst, a clinical geneticist who worked at a hospital on Oxford's grounds and, coincidentally, had coauthored the first report on the KE family.


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