Much interest in dysbindin has arisen through pedigree-based family-association studies of families with a history of schizophrenia, where a strong association was found between expression of a particular dysbindin allele and a clinical expression of schizophrenia. However, the genetic link between dysbindin and schizophrenia has not been established in all the case control samples tested and this implies that there are different genetic subtypes of schizophrenia with different disease allele frequencies in different populations. This phenomenon is called genetic locus heterogeneity and is typical of all common disorders with a strong genetic component. A further complication is that it is highly likely that there are several or many different mutations within the dysbindin gene that are responsible for schizophrenia. This complexity is called disease allele heterogeneity and is a further reason that genetic associations are found with different markers in the dysbindin gene when different samples are studied.
Genetically caused dysbindin-related mechanisms causing brain dysfunction are not fully known, but in one study, schizophrenic patients carrying the high-risk haplotype demonstrated visual processing deficits. In another work, damping down the DTNBP1 expression led to an increase in cell surface dopamine D2-receptor levels.
^ abcBenson et al.; Newey, SE; Martin-Rendon, E; Hawkes, R; Blake, DJ (2001). "Dysbindin, a novel coiled-coil-containing protein that interacts with the dystrobrevins in muscle and brain". J Biol Chem276 (26): 24232–41. doi:10.1074/jbc.M010418200. PMID11316798.
^Straub et al.; Jiang, Y; MacLean, CJ; Ma, Y; Webb, BT; Myakishev, MV; Harris-Kerr, C; Wormley, B et al. (2002). "Genetic Variation in the 6p22.3 Gene DTNBP1, the Human Ortholog of the Mouse Dysbindin Gene, Is Associated with Schizophrenia". Am J Hum Genet71 (2): 337–48. doi:10.1086/341750. PMC379166. PMID12098102.|displayauthors= suggested (help)
^Donohoe G, Morris DW, De Sanctis P, Magno E, Montesi JL, Garavan HP, Robertson IH, Javitt DC, Gill M, Corvin AP, Foxe JJ (2007). "Early Visual Processing Deficits in Dysbindin-Associated Schizophrenia". Biol Psychiatry63 (5): 484–9. doi:10.1016/j.biopsych.2007.07.022. PMID17945199.
^Iizuka Y, Sei Y, Weinberger DR, Straub RE (2007). "Evidence that the BLOC-1 protein dysbindin modulates dopamine D2 receptor internalization and signaling but not D1 internalization". J. Neurosci.27 (45): 12390–5. doi:10.1523/JNEUROSCI.1689-07.2007. PMID17989303.
^Li W, Zhang Q, Oiso N, Novak EK, Gautam R, O'Brien EP, Tinsley CL, Blake DJ, Spritz RA, Copeland NG, Jenkins NA, Amato D, Roe BA, Starcevic M, Dell'Angelica EC, Elliott RW, Mishra V, Kingsmore SF, Paylor RE, Swank RT (2003). "Hermansky-Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1)". Nat. Genet.35 (1): 84–9. doi:10.1038/ng1229. PMC2860733. PMID12923531.
^ abcStarcevic M, Dell'Angelica EC (July 2004). "Identification of snapin and three novel proteins (BLOS1, BLOS2, and BLOS3/reduced pigmentation) as subunits of biogenesis of lysosome-related organelles complex-1 (BLOC-1)". J. Biol. Chem.279 (27): 28393–401. doi:10.1074/jbc.M402513200. PMID15102850.