Association study on the DUSP6 gene, an affective disorder candidate gene on 12q23, performed by using fluorescence resonance energy transfer-based melting curve analysis on the LightCycler

We introduced a new genotyping method, fluorescence resonance energy transf er-based melting curve analysis on the LightCycler, for the analysis of the gene, DUSP6(dual specificity MAP kinase phosphatase 6), in affective disor der patients. The DUSP6 gene is located on chromosome 12q22-23, which overl aps one of the reported bipolar disorder susceptibility loci. Because of it s role in intracellular signalling pathways, the gene may be involved in th e pathogenesis of affective disorders not only on the basis of its position but also of its function. We performed association analysis using a T>G po lymorphism that gives rise to a missense mutation (Leu114Val), No evidence for a significant disease-causing effect was found in Japanese unipolars (n = 732) and bipolars (n = 122), when compared with controls (n = 299). More importantly, this study demonstrates that melting curve analysis on the Li ghtCycler is an accurate, rapid and robust method for discriminating genoty pes from biallelic markers. This strategy has the potential for use in high throughput scanning for and genotyping of single nucleotide polymorphisms (SNPs).