|
 |
|
      |
|
|
|
 Research & Giving News Article  Team Also Specifically Links Three Deleted Segments to Illness For several decades, scientists have known from studies of identical and fraternal twins that schizophrenia has a strong genetic component, which has been estimated to account for about 80 percent of risk. But they have searched largely in vain for commonly occurring gene mutations that would explain the prevalence of the disease in the general population -- about one in every 100 people. It has been widely assumed that a relatively small number of commonly occurring gene mutations, each producing a small effect but assumed to be acting in concert with one another and also with environmental factors, triggers many cases of schizophrenia. The new study, led in part by Pamela Sklar, M.D., Ph.D., a two-time NARSAD Young Investigator and recipient of an Independent Investigator award, suggests another important genetic factor contributing to risk for schizophrenia. Based on genome scans of 3,391 patients and 3,181 healthy controls, the study found that patients were more likely to have rare gene mutations of a particular kind, called copy number variations, or CNVs. CNVs are segments of the genome, sometimes but not always containing one or more genes, that for unknown reasons are either deleted or repeated in a person. CNVs can be inherited or occur “spontaneously,” in a child whose parents do not have the missing or repeated genome segments. Certain instances -- but not all -- of these “structural variations” of the chromosomes are theorized to disturb gene expression, perhaps triggering serious illness. CNVs Are More Common in Patients Than Controls After comparing genome scans of healthy people and people with schizophrenia, the scientists noted a key pattern: people who had these rare chromosomal deletions and duplications were more likely to have the illness. As Dr. Sklar -- of Massachusetts General Hospital, Harvard University and MIT’s Broad Institute -- and her colleagues in the International Schizophrenia Consortium reported last week in an advance online edition of the journal Nature, the increased schizophrenia risk associated with possessing a rare CNV is “subtle” -- 1.15 times the risk of people who don’t have this type of structural mutation in their genome. When they counted only instances where CNVs contained a gene, the team found a larger difference in risk between patients and healthy people: patients had such mutations 1.41 times as often as people in the control group. CNV-Disease Link Is Not Understood One question raised by this research concerns the precise nature of the relation between CNVs and biological processes that contribute to schizophrenia. “Exactly how” the additional risk associated with having CNVs “translates mechanistically into illness in a given patient is currently unknown,” the scientists noted. They added: “Similarly, we do not know how environmental risk or protective factors might act in concert with specific CNVs” to cause illness. The consortium’s scientists, like researchers who have found CNVs in other schizophrenia populations, are intrigued by the fact that some of the genes in the deleted or repeated areas have separately been associated with other neurobiological disorders, including mental retardation, psychosis, bipolar disorder and autism. Researchers have begun the difficult task of determining how specific CNVs affect the expression of genes, which, in turn, may be parts of networks that might affect function of the brain and other aspects of the human system. Such changes, in turn, could have an impact on risk for schizophrenia and other mental illnesses including autism and bipolar disorder. Study Also Links Three Specific Deleted Regions to Schizophrenia The International Schizophrenia Consortium’s genome scans also identified three deleted regions in the genome that it specifically linked to schizophrenia, including an area on chromosome 22 that has been identified in other studies. The other two deletions, though, had not been previously implicated in the disease: large sections of DNA on chromosomes 1 and 15 were missing more often in patients with schizophrenia than in controls. In another study appearing in the same issue of the journal Nature, a team of researchers led by scientists at deCODE Genetics found that the same three deletions conferred risk for the disorder, in effect an independent confirmation of the consortium’s finding. “In light of these new findings,” Dr. Sklar commented on the work on CNVs, “there no longer needs to be an argument that this type of variation plays a role in some of the risk” for schizophrenia. “The task now is to understand how rare structural variation, together with other kinds of genetic variation and environmental effects, work together to produce schizophrenia.” Parts of this story were adapted by NARSAD with permission of the Broad Institute in Cambridge, Mass. |
Media Contact
Latest News from NARSAD
Spotlight
|
|
For the Media