SCREENING THE DOPAMINE D-1 RECEPTOR GENE IN 131 SCHIZOPHRENICS AND 8 ALCOHOLICS - IDENTIFICATION OF POLYMORPHISMS BUT LACK OF FUNCTIONALLY SIGNIFICANT SEQUENCE CHANGES

To determine whether mutations in the D-1 dopamine receptor (D-1 DR) gene are associated with schizophrenia, the coding sequence was examined in 106 Caucasian, 11 African-American, 8 Asian, and 6 Native American patients, Approximately 350 kb of genomic sequence was screened by dideoxy fingerprinting, a method related to single strand conformational polymorphism (SSCP) analysis that detects virtually 100% of sequence changes [Sarkar et al., 1992: Genomics 13:441-443; Liu and Sommer, 1994: PCR Methods and Applications 4:97-108]. One polymorphism was identified in Asians and one in Caucasians, but neither altered the amino acid sequence (Leu(66), and Ser(421), respectively), In addition, a previously reported polymorphism in the 5' untranslated region of exon 2 at bp -48 was found to be common, with an allele frequency of approximately 40% in Caucasians of Western European descent, Based on the fact that no sequence changes of likely functional significance were identified, these data suggest that mutations affecting the structure of the D-1 dopamine receptor protein are uncommon and are unlikely to contribute significantly to the genetic predisposition to schizophrenia, The D(1)DR gene also was examined in eight alcoholics, including 3 African-Americans and 1 Native American, but no sequence changes were identified. (C) 1995 Wiley-Liss, Inc.