A team of researchers from the Wellcome Trust Sanger Institute, the Broad Institute of MIT and Harvard and the Institute for Molecular Medicine Finland, found that a disruption of the gene TOP3B, an exceedingly rare occurrence in most parts of the world, is fairly common in a uniquely genetically distinct founder population from North-eastern Finland.
Furthermore, the biochemical investigation of the protein encoded by the TOP3B gene allowed the researchers to gain first insight into the cellular processes that might be disturbed in the affected individuals.
The team identified a rare genetic deletion affecting TOP3B in the North-eastern Finnish population that increases a person's susceptibility to schizophrenia two-fold and that also is associated with an increased frequency of other disorders of brain development such as intellectual impairment. They speculate that this deletion directly disrupts the TOP3B gene to cause its effects on the brain.
Having identified the link between TOP3B and schizophrenia, the researchers sought to understand why disrupting this gene might increase susceptibility to disease, and for this purpose they investigated the function of the protein that it encodes.
TOP3B encodes a type of protein that typically helps the cell to unwind and wind DNA helices - essential to normal cell function. Quite unexpectedly for an enzyme of this class, however, TOP3B was found to act on messenger-RNA rather than DNA.
In their further biochemical investigation into TOP3B, the team found that the TOP3B protein interacts with a protein known as FMRP. The deactivation or disruption of this protein is responsible for Fragile X syndrome, a disorder associated with autism and learning difficulties, primarily in men.