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CSHL scientists part of team that discovers role of rare gene mutations in schizophrenia
Date:3/28/2008

Using an important new method that can be applied in the study of other psychiatric illnesses, scientists at Cold Spring Harbor Laboratory (CSHL) in collaboration with colleagues at the University of Washington (UW) and the National Institute of Mental Health (NIMH), have identified multiple, individually rare gene mutations in people with schizophrenia that may help explain how that devastating illness is caused.

The team screened for novel deletions and duplications in the genome -- what are called gene copy-number variations, or CNVs. They found that deletions, disruptions and duplications of normal genes, most of them rare, were three to four times more frequent in people with schizophrenia than in controls.

CSHLs contribution to the research effort was led by Assistant Professor Jonathan Sebat, Ph.D., and Shane E. McCarthy, Ph.D. Drs. Tom Walsh, Jon McClellan and Mary-Claire King led the UW team, while Drs. Anjene Addington and Judith Rapoport led the researchers at NIMH.

A New Method of Finding Candidate Genes

The researchers used a novel method to study their two-cohort sample, which included 418 individuals, 150 of whom had schizophrenia or schizoaffective disorder. Instead of trying to show a statistical correspondence between a large group of people with schizophrenia and irregularities in common versions of genes, the team began by looking for glitches or changes in DNA that are likely to disrupt gene function. Then they compared which genes -- with what kinds of functions -- were impaired, both in the healthy subjects and those with schizophrenia.

The results were striking. Rare mutations showed up in only 5 percent of the healthy controls versus 15 percent of those with schizophrenia. The rate of rare mutation was higher still -- 20 percent -- among an early-onset subset of patients, who had developed schizophrenia before age 19.

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Contact: Jim Bono
pubaff@cshl.edu
516-367-8455
Cold Spring Harbor Laboratory
Source:Eurekalert

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