Professor David Lewis outlines how microarrays have transformed the search for schizophrenia genes and led to his group's discovery of the candidate gene, RGS4.
The development, about ten years, of cDNA microarrays, which provide the ability to look simultaneously at the levels in a given brain region of messenger RNAs, or the immediate products of genes, has made it possible to virtually examine, at one time, all of the products of the entire genetic code - to ask, which ones of these are disturbed in schizophrenia?
A major advantage of this approach is that it made it possible to do what some have called discovery science, or others, such as ourselves, have referred to ask ignorance-based research, meaning we really don’t know what the underlying problem is, so we want to apply a very powerful tool that enables us to look at multiple things simultaneously to look for leads as what is disturbed.
So, for our group, one of the findings that came out of an initial microarray study was an observation of an alteration in a particular gene called RGS4, or regulator of gene signaling protein 4, that had previously not been considered at all in schizophrenia, which has now been found to not only be disturbed at the level of the gene product, but perhaps also to be disturbed at the level of the gene itself. While the data are still not conclusive, there is at least a suggestion that RGS4 may be a risk gene for schizophrenia.