Possible Schizophrenia Gene Identified

30 October 1997 8:00 pm

Scientists have found a human gene that may boost the risk of developing schizophrenia and other mental disorders. The researchers plan to announce their discovery tomorrow morning at the annual meeting of the American Society of Human Genetics in Baltimore, Maryland. If their hypothesis holds up, it could open an important avenue to understanding the genetics of schizophrenia, a crippling illness that affects 1% of the population.

It was "a fortuitous turn of events" that led to this newly identified gene, says molecular geneticist George Gutman of the University of California, Irvine (UCI). His colleague George Chandy was sifting a database for information on DNA that controls potassium channels in neurons, says Gutman, when he noticed a curious fact: Two papers mentioned a repeated three-letter genetic sequence (CAG) in human DNA linked to the genetic material he was interested in. By making a comparative database study of rat DNA, the UCI team identified the source of the anomaly--a gene that regulates a cellular potassium channel, which in turn regulates electrical activity in the brain. They named the gene hSKCa3.

Gutman says that he, Chandy, and colleague Jay Gargus immediately recognized the significance of the find: Repeated CAG sequences in the human genome are known to be involved in neurological disorders, such as Huntington's disease. What's more, hSKCa3 turned out to be on chromosome 22, in a region that some researchers had already associated with schizophrenia. The UCI group then formed a collaboration with the University of Pittsburgh and two European centers to check for an association between CAG repeats in this gene and schizophrenia in people. In a study comparing more than 100 schizophrenic patients with healthy controls, they found that the patients had more of the CAG repeats than did the healthy people--in one patient, up to 28 CAG repeats. Now, says Gutman, "we need to look at a larger and more diverse population" to see if this association holds up.

Psychiatrist Kenneth Kendler of the Virginia Commonwealth University in Richmond, a longtime leader in the search for schizophrenia genes, is "intrigued" by the UCI report, but remains cautious about it. The statistical significance, Kendler says, is "modest," and appears to be derived from a slightly "old fashioned" method of analysis. His advice: "Let's wait and see if anybody else can replicate it."

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