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Collaborations yield new discoveries in psychiatric genetics

Millonig said. "Identifying a gene in a complex disease may give more insight into the pathways involved it helps you begin to unravel what is at its basis."

Earlier genetic studies of a Canadian study population of large families with a high incidence of schizophrenia pointed the way to CAPON. The gene was known to code for a protein that functioned in a neuronal pathway thought to be linked to schizophrenia. Beyond establishing a mere statistical connection between a gene and a psychiatric disorder CAPON and schizophrenia Firestein and Brzustowicz provided functional evidence as to the nature of the connection. "We began with a purely genetic approach and identified a region of chromosome 1 that seemed very likely to contain a susceptibility gene, but then moved on to studies of gene expression in human brains to search for convincing evidence of a functional role for CAPON in schizophrenia," Brzustowicz said.

The researchers discovered two forms of the gene are normally expressed in human brain, a long form and a short form. Based on what is known about the gene interactions, it is predicted that when the short form is present in excess, it will disrupt the signaling pathway, resulting in decreased function, reduced signaling and less communication, all of which are suspected to occur in schizophrenia, Firestein said. The published information includes a detailed description of how this is thought to occur.

The research team then analyzed the post-mortem brains 35 from individuals with schizophrenia, 35 from bipolar individuals and 35 from those with normal brains and found significantly increased levels of the short form in the specimens from individuals with psychiatric disorders.

While many genes have been implicated in schizophrenia based on family studies, there has been little functional evidence for alteration in the proteins that are actually involved, but with CAPON there does, indeed, appear to be functional evide
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Contact: Joseph Blumberg
blumberg@ur.rutgers.edu
732-932-7084 x652
Rutgers, the State University of New Jersey
6-Oct-2005


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