Functional Analysis of the Human D2 Dopamine Receptor Variants We have previously described three DNA variations in the dopamine D2 receptor gene that predict substitutions in the amino acid sequence of the receptor (Val96 to Ala96, Pro310 to Ser310, and Ser311 to Cys311) (Gejman et al., 1994). We have expressed these variants in stable cell lines and have now defined their biochemical phenotype. The substitutions Cys311 and Ser310 failed to normally reduce cAMP concentration of forskolin-induced cAMP levels, a critical intracellular event mediated by this receptor. Methodology of Mutational Analysis Prospective blind study of detection of unknown mutations shows that denaturing gradient electrophoresis is robust for the screening of mutations in long DNA segments (>500bp). Candidate Gene Analysis 1. No evidence found for association between dopamine D3 receptor (DRD3) gene or dentarubral-pallidoluysian atrophy (DRPLA) gene and schizophrenia. 2. Association and linkage showed that the alpha stimulatory subunit of the G protein is not involved in bipolar disorder. Ascertainment and collection of clinical specimens Neuroleptic Malignant Syndrome: 14 cases collected.1.
