Instead, BMN 673 nmr several studies report a differential gene expression in cases versus controls in target areas of the brain for NRG1 and DTNBP1; given that associated alleles/haplotypes are located in introns, it can be suggested that the pathogenic mutations induce a regulatory dysfunction. The meaning of the variation of haplotypes across studies is currently not appropriately understood. Two Inhibitors,research,lifescience,medical putative interpretations are possible: Different “causal” mutations in the same gene contribute to the emergence of schizophrenia; these mutations are not yet known; different “causal” mutations

might predominate in different samples due to “genetic heterogeneity” of schizophrenia; significant associations Inhibitors,research,lifescience,medical to different haplotypes may be a consequence. Linkage disequilibrium between positional markers is variable across populations and samples; thus, the positional markers in linkage disequilibrium with the same “causal” mutations are different between populations and samples. It is currently not possible to decide which of both options Inhibitors,research,lifescience,medical is true. In any case, it is very unlikely that

the disparity between associated haplotypes of the gene reflects a “false positive” finding. Alternative successful strategies Two alternative strategies have also turned out to be successful: Cytogenic analyses in isolated families highly loaded with schizophrenia: A translocation was detected Inhibitors,research,lifescience,medical to cosegregate with the condition status in the family.6 A specific gene (not previously known) on chromosome 1 was regularly disrupted, and was named DISC1. Surprisingly, common mutations in this gene were also found to be associated Inhibitors,research,lifescience,medical with schizophrenia in outbred populations.7 Gene expression might guide to susceptibility genes: Given the plethora of differentially expressed genes in postmortem brains of patients with schizophrenia, specific hypotheses are required to sharpen the focus to differentially expressed

genes for further study. Assuming that synaptic and postsynaptic transmission is a crucial feature of schizophrenia, phosphokinases present as a family of candidate proteins; polymorphic genes coding for these units of intracellular signal transmission thus became “hot” candidate genes. These DNA-sequence (-)-p-Bromotetramisole Oxalate variants in the differentially expressed protein kinase B (AKT1) were found to be associated with schizophrenia.8 Several replications of the original finding have now been published.9 The detected susceptibility genes throw light on the etiology and the pathophysiology of schizophrenia. None of the abovementioned detected candidate genes has been implicated in the development of schizophrenia before.