Schizophrenia Linked to a Large Number of Different Gene Defects
Scientists from the University of Washington have located gene abnormalities that could explain how schizophrenia develops in some patients. Researchers identified gene deletions and extra (duplicated) segments of DNA which are more frequent in people with the schizophrenia. It was discovered that abnormalities occur in genes related to the development of the brain and brain function. These discoveries,were confirmed by other researchers from the National Institute of Mental Health.
Schizophrenia is a serious psychiatric disorder that occurs in approximately 1 percent of the population. Features of schizophrenia include hallucinations, disorganized thinking and delusions. Patients with the disorder also may show bizarre behaviors. Schizophrenia causes enormous social and financial costs as well as a large amount of suffering for patients and their families.
The scientists looked at genetic errors, including rare DNA deletions and duplications to see how they affect the development of schizophrenia.
A variety of DNA segment deletions and duplications occur in all humans and other animals. The team of investigators examined mutations that occur only in patients with the schizophrenia, and compared them to DNA abnormalities that found only in healthy persons. Researchers looked for unusual mutations that were unique to schizophrenic patients. Mutations in genes that regulate brain growth and function were thought to be likely causes of problems in patients with schizophrenia.
DNA samples from 150 patients suffering from schizophrenia and 268 healthy individuals were sequenced. Researchers identified unusual DNA deletions and duplications in 15 percent of those with schizophrenia, versus only 5 percent in the healthy controls. The rate of these unusual DNA abnormalities was even higher in patients who developed schizophrenia at an early age. As many as 20 percent of patients with an early onset of the disease had the unusual mutations.
In patients with schizophrenia, DNA problems were more likely to disrupt genes that help to control brain development. Each of the mutations was different, and impacted different genes. Several of the disrupted genes control neural pathways.
This research suggests that schizophrenia is caused by many different mutations in many different genes. Each mutation disrupts an important pathway that regulates brain growth and development. Once a disease-causing mutation is identified, other different disease-causing mutations may be found in the same gene in different people with the illness.
Thus, for most cases of schizophrenia, the genetic causes may be different. This observation has important implications for schizophrenia research. Currently, most genetic studies examine for mutations that are shared among different individuals with the illness. These approaches will not work if most patients have different mutations causing their condition.
Fortunately, there are now genomic technologies available that allow researchers to discover rare mutations within each individual with a disorder. As these technologies improve, it will be possible to detect other types of disease-causing mutations. Eventually, the identification of genes disrupted in individuals with schizophrenia will allow the development of new treatments more specifically targeted to disrupted pathways.
ref:http://uwnews.org/article.asp?articleID=40615
