Gene variation raises risk of bipolar disorder and schizophrenia

function of the genes that cause a disease in order to find them. Once found, however, the gene's function can be elucidated.

"Instead of interrogating the usual suspects, positional cloning leads us to novel genes," said Gershon, "and novel genes provide new information, which could help us find better treatments."

The team, headed by research associates Eiji Hattori and Chunyu Liu in Gershon's laboratory, studied two large series of families in which several members have bipolar disorder. The Clinical Neurogenetics pedigrees include 371 individuals from 22 extended families. The National Institute of Mental Health Genetics Initiative pedigrees include 474 individuals from 152 families.

Both series provided strong evidence that one version of a stretch of DNA that includes the two genes was associated with bipolar disorder. This consistency lends power to the finding.

G30 and G72 are "rather strange genes," said co-author Hattori. They are expressed only in primates, with no counterpart in mice. They have no known function. They reside in a sort of "gene desert," near the end of the chromosome, with no other genes nearby, and they overlap on complementary chromosome strands.

The G72/G30 gene complex was discovered at Genset Corporation, which reported association of this complex with schizophrenia in the fall of 2002.

These two reports are the first consistent demonstration of a gene complex associated with both bipolar illness and schizophrenia. For a century, these disorders were thought to be inherited separately. In the past few years, however, the possibility that the same genes contribute to both disorders has gained favor.

One other gene has been implicated in bipolar disorder. In 2002, researchers found that brain-derived neurotrophic factor, a candidate gene, was associated with the disease.


Contact: John Easton
University of Chicago Medical Center

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