DISC1 is now well established as what Tom Insel, Director of the U.S. National Institute of Mental Health, has termed an “edge piece” of psychiatric genetics. Many studies have reported effects of DISC1 genetic variation on a spectrum of psychiatric disorders, including and extending beyond the schizophrenia, bipolar disorder, unipolar depression, and adolescent conduct disorder reported in the original Scottish family with a balanced t(1;11) translocation through which DISC1 was identified. The neurodevelopmental and neurosignaling roles of DISC1 are increasingly well understood through the scaffold function of DISC1, including GSK3β, PCM1, PDE4, NDE1, and NDEL1, to name but some of the currently most interesting and well studied interactors that are illuminating normal and pathogenetic brain processes. (See Brandon et al., 2009; Porteous and Millar, 2009; Jaaro-Peled et al., 2009; and Chubb et al., 2008 for more background and review summaries.)
The focus of this meeting will be as follows:
1. Update on animal models: What are these models telling us about the neurobiology of DISC1? What are the key DISC1-associated behavioral phenotypes? What kinds of criteria, including histological and molecular hallmarks, are most relevant to translational research? What experiments still need to be done? What other models are needed?
2. Update on DISC1 genetics: What is the status on evidence for common risk variants and rare mutations in the DISC1 pathway? What do these tell us about genotype-phenotype relationships? What do they tell us about structure-function relationships?
3. Update on DISC1 signalosome: What underlies the temporal and spatial specificity of DISC1 pathways in brain circuitry, such as isoform disposition, post-translational modifications, and different combinations of protein interactors?
We now invite your comments in advance of the live discussion and look forward to your participation.
See also DISC1 Roundtable 2009 and The DISC1 Pathway in Major Mental Illness: Clinical, Genetic and Biological Evidence—Current Status and Future Prospects.