Most common diseases are associated with subtle changes in a large number of genes. But every once in a while, scientists succeed in linking certain cases of an illness to mutations of a single gene. When this occurs, when it turns out that one renegade gene has derailed an otherwise healthy person, scientists often learn something crucial about an illness and move closer to defeating it.
In pursuit of this goal, scientists at the School of Medicine and the School of Public Health, led by Pei-Lung Chen, have undertaken a genetic analysis of schizophrenia. They have found a gene, neuregulin-3 (NRG3), that appears to be associated with certain aspects of schizophrenia.
Using previous studies that implicated a certain region of genes on chromosome 10 as a possible hot spot of schizophrenic activity, Chen and colleagues analyzed snippets of DNA from a region of the chromosome in both affected persons (those with schizophrenic symptoms) and controls (those who are unaffected).
Most genes have more than one version, called an allele. These alleles usually differ by relatively small changes in the sequence of letters that specifies the genetic code.
By seeing which alleles these two groups share and which ones are different, Chen and colleagues have found that alterations in NRG3 seem to be responsible for at least one set of symptoms in some schizophrenic patients, the delusions that are often a hallmark of the disease.
Chen's group did not identify specific mutations or variants in NRG3, but rather, showed that variability at this site is linked to schizophrenia delusions. Mutation analysis will come later.
Neuregulin-3 is one of many proteins involved in directing the "wiring" of the nervous system during development and into adulthood. Since many scientists believe that schizophrenia is the result of a mis-wired nervous system, the finding of mutations in NRG3 is not surprising, and opens up new possibilities for treatment.
Although the team has identified a reliable relationship for the NRG3-delusions correlation, not all schizophrenia symptoms have been linked to genetic defects, and certainly this team has not found any one so called "schizophrenia" gene. It is more likely that a certain constellation of gene defects come together in such a way that a diagnosis of "schizophrenia" can be made based on the exhibited symptoms.
Indeed, this makes much more sense than one singular "schizophrenia gene," as schizophrenia happens to be a disorder in which there is a lot of variety; not every patient's profile is exactly the same as the next's.
But there are certain core symptoms that seem to be consistent across many patients' profiles, and so it is these traits that are the most fruitful in terms of finding a gene-disorder link. Other symptoms may just be the large-scale residues of extraneous genetic mix-ups.
Thinking about one gene, one disorder without regard can be dangerous. It can lead to oversimplification of disorders and phenomena seen in biological systems.
Nevertheless, it's obvious that genes play a huge role in just about every aspect of an organism, and many disorders, like schizophrenia, seem to have at least some genetic component - it is known that schizophrenia often runs in families, for instance.
This study, and related ones that are still ongoing, will hopefully offer new targets for understanding the genesis and treatment for schizophrenia and a range of other disorders.