Dysbindin and Schizophrenia

Professor Daniel Weinberger discusses research that makes dysbindin a candidate gene for schizophrenia.

The gene that probably has the best track record of showing that it increases risk for schizophrenia in populations all over the world is dysbindin. So dysbindin was discovered based on family studies from Ireland that looked within families at whether there regions of the genome, in these so-called linkage studies, that produced evidence that a gene was found in that region that would be explaining the existence of schizophrenia in these families. This was the whole genetic linkage strategy, which I'm not going to go into here. The region of the genome that showed the best so-called linkage signal in those families was a region on the short arm of the sixth chromosome. And then ultimately that region was interrogated using the human genome project DNA human genome sequence, and a gene dysbindin was found to lie in this region. And then subsequent studies were done to see if changes in the gene sequence, that is dysbindin sequence variance, were more frequent in patients with schizophrenia than in control samples. This has now been found in over ten studies in populations all over the world. So dysbindin is a very, very strong candidate for being a schizophrenia susceptibility gene. What does dysbindin do to make it a susceptibility gene? This is work that is just really gaining momentum because nobody knew about dysbindin as a gene related to schizophrenia until two years ago. So there's a lot of work being done right now to try to understand how dysbindin impacts on the frontal lobe and the hippocampus and other important biological aspects of schizophrenia to become a risk gene.