DISC1 - Research Directions

Research Directions

As DISC1 investigation continues to be an emerging area of study, many unanswered questions regarding the biological function of the protein and its implications in psychiatric disorders remain. In depth understanding of DISC1 as a genetic risk factor for psychiatric disorders provides a possible target for developing new drug therapies and preventative measures. The pathways regulated by DISC1 interaction may provide possible avenues for therapeutic opportunities to reverse related deficits. Definitive genetic architecture, risk distribution, and their correlation with prognosis is crucial to determining response to new drug treatments.

In addition to DISC1, the antisense partner has been identified as DISC2, a noncoding RNA gene that may be involved in regulating the gene locus. However, structure and function of DISC2 remain unknown and may provide insight into how DISC1 is regulated.

Rare mutations in DISC1 other than the original translocation have been discovered and require further investigation. Furthermore, posttranslational processing and its effect on isoform expression, which also contributes to protein function and may be involved in some forms of disease, remains to be studied. The ability to predict the impact of different types of mutations on protein function and resulting psychiatric phenotype is crucial for the development of targeted treatments.

Family studies continue to provide an important approach towards deepening understanding of the biological nature of the gene and its clinical implications. While the original Scottish family in which DISC1 was discovered is still being considered, other familial populations in different countries have also become the focus of research in the past decade. In 2005, an American family was found to also possess a frameshift mutation in the DISC1 gene, which again co-segregated with schizophrenia and schizoaffective disorder. Characterized by a deletion of four base-pairs, the mutation was found in two siblings, one with schizophrenia and the other with schizoaffective disorder. Similar studies have also been done with Taiwanese and Finnish families.