Scientists localize susceptibility gene for schizophrenia

April 26, 2000

Researchers believe they have localized a major susceptibility gene for schizophrenia on chromosome 1, according to a study published in the April 28 edition of the journal Science.

Led by Dr. Anne Bassett, the study's senior author, researchers collected DNA samples and over a 12-year period assessed 300 individuals from 22 Canadian families with a high incidence of schizophrenia, a serious psychiatric illness that affects one per cent of the general population.

Bassett and her colleagues believe there are several genes involved and there may be environmental factors that interact to ultimately cause the illness. "Even though schizophrenia is complex, we decided to look for rare families where the illness looked like it was being inherited. The families participating in the study are key -- they are large and have two or more members with schizophrenia," says Bassett, an associate professor of psychiatry at the University of Toronto and head of the Schizophrenia Research Program at the Centre for Addiction & Mental Health (CAMH).

"If we compare the human genome to a map of the world and gene localizing to finding the neighbourhood the gene lives in, previous studies have been able to say that there may be a gene in North America, maybe even in Canada," she says. "Our study tells us that there is a gene predisposing to schizophrenia in the neighbourhood of downtown Toronto and that we should be able to pinpoint the exact location in the next step of the research."

Using a lod score analysis -- the same method used to locate genes for breast cancer -- the study's lead author, Dr. Linda Brzustowicz of Rutgers University in New Jersey, located a schizophrenia susceptibility gene in a small region of chromosome 1, likely the "address" of the susceptibility gene. "This finding is very strong," Brzustowicz says. "This is approximately 100 times stronger evidence for the existence of a schizophrenia gene than reported in previous studies."

The magnitude of the chromosome 1 result gives scientists realistic hope that further research will lead them to the schizophrenia gene that is in this region of the human genome. "These results should pave the way for discovering the other genes and environmental factors which may play a role in schizophrenia," says Bassett, who initiated this study 12 years ago while on a research fellowship at the New York State Psychiatric Institute with Brzustowicz and another of the study's authors, Dr. William Honer, now at the University of British Columbia.

The authors believe knowing about the nature and function of genes will provide insights into the underlying biological mechanisms of schizophrenia and should lead to improved treatments for the disease. Other researchers involved in this study are Dr. Eva Chow, assistant professor of psychiatry at U of T and a research psychiatrist at CAMH and Kathleen Hodgkinson, a genetic counsellor and graduate student at the centre.

This research, which has involved longstanding multicentre and multidisciplinary teamwork, has received funding from Canadian and American sources over the past 12 years. These include: the Medical Research Council of Canada, Ontario Mental Health Foundation, Bill Jefferies Research Foundation, Ian Douglas Bebensee Foundation, EJLB Foundation, Scottish Rite Schizophrenia Research Program, National Institute of Mental Health, Center for Inherited Disease Research, National Alliance for Research on Schizophrenia and Depression, and individual donations.

The Centre for Addiction and Mental Health, a World Health Organization Centre of Excellence and a teaching hospital fully affiliated with the University of Toronto, was established in 1998 through the merger of the Addiction Research Foundation, the Clarke Institute of Psychiatry, the Donwood Institute and the Queen Street Mental Health Centre.

Steven de Sousa
U of T Public Affairs

University of Toronto

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