Identification and characterisation of SNPs in candidate genes for schizophrenia

Improvements in molecular genetic technology and the progress of the Human Genome Project now allows us to replace limited candidate gene studies with almost complete systems-based tests of alternative hypotheses of aetiology of psychiatric disorders. As part of a systematic analysis of the glutamatergic and GABAergic hypotheses of schizophrenia we have surveyed over 25 candidate genes for sequence variation. In order to achieve this we have used either their previously deduced genomic structures or the available human genome sequence data to predict the intron/exon boundaries of genes. The 5′and 3′UTR's together with the coding sequence for all genes have been screened for sequence variants using dHPLC heteroduplex analysis in a sample of 14 schizophrenic patients, and the resulting SNP's characterized using Big Dye(tm) sequencing. Thus we have identified a panel of SNP's spanning each candidate gene. As well as being useful for direct candidate gene analysis and indirect LD mapping studies for schizophrenia and other disorders including, epilepsy and Alzheimer's disease, these SNP's are also of potential interest in studying sequence variation in human genes.