DISC1 and DISC2: discovering and dissecting molecular mechanisms underlying psychiatric illness.
A balanced (1;11)(q42;q14) translocation co-segregates with schizophrenia and major affective disorders in a large Scottish family. The translocation breakpoint on chromosome 1 is located within the Disrupted in Schizophrenia 1 and 2 genes (DISC1 and DISC2). Consequently loss of normal function of these genes is likely to underlie the susceptibility to developing psychiatric disorders that is conferred by inheritance of the translocation. Additionally, a number of independent genetic studies highlight the region of chromosome 1q containing DISC1 and DISC2 as a likely susceptibility locus for both schizophrenia and affective disorders. These genes are thus implicated in the aetiology of major psychiatric disorders in several populations. Although the function of DISC1 was initially unknown, several recent reports have made significant progress towards understanding its role in the central nervous system. Intriguingly, all data obtained to date point towards an involvement in processes critical to neurodevelopment and function. DISC2 has not been studied in detail, but is likely to modulate DISC1 expression. Overall, it is clear from the combination of genetic and functional data that DISC1 and/or DISC2 are emerging as important factors in the molecular genetics of psychiatric illness.
Medical Genetics Section, Department of Medical Sciences, The University of Edinburgh, Edinburgh, UK. Kirsty.Millar@ed.ac.uk
J Kirsty
JK
Millar
Rachel
R
James
Nicholas J
NJ
Brandon
Pippa A
PA
Thomson
D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D019964:Mood Disorders / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D012559:Schizophrenia / Q000235:genetics*; D014178:Translocation, Genetic; D025521:Tumor Suppressor Proteins / Q000235:genetics
D002352:Carrier Proteins; C412476:DISC1 protein, human; C448722:DISC2 gene product, human; D004268:DNA-Binding Proteins; C118711:LZTS1 protein, human; C421108:NDEL1 protein, human; D009419:Nerve Tissue Proteins; D062085:RNA, Long Noncoding; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins