We search for expressed DNA variations (DNA variations that affect the amino acid structure) in candidate genes (genes thought to be involved in the pathophysiology Of psychiatric disorders). Methods for large scale screening of many individuals for mutations in candidate genes for psychiatric disorders are needed for two reasons: (l) existence of numerous plausible candidate genes and, (2) possible genetic heterogeneity. We currently employ denaturing gradient gel electrophoresis (DGGE) for the large-scale molecular scanning of mutations. We have screened the complete coding sequences of the dopamine D2 receptor gene for mutations in schizophrenia (n=106), alcoholism (n=ll3), in a pharmacological trait: the malignant neuroleptic syndrome (n=9) and in controls. Three expressed DNA variants were found. No DNA variant was associated with disease. Therefore, the hypothesis is ruled out that a change in the coding sequences of the gene for DRD2 is associated with alcoholism or schizophrenia in any meaningful proportion of cases. In vitro expression and analysis of the discovered variants will determine the existence of functional correlations.
