SYSTEMATIC SCREENING FOR MUTATIONS IN THE PROMOTER AND THE CODING REGION OF THE 5-HT1A GENE

In the present study we sought to identify genetic variation in the 5- HT1A receptor gene which through alteration of protein function or lev el of expression might contribute to the genetic predisposition to neu ropsychiatric diseases. Genomic DNA sam ples from 159 unrelated subjec ts (including 45 schizophrenic, 46 bipolar affective, and 43 patients with Tourette's syndrome, as well as 25 healthy controls) were investi gated by single-strand conformation analysis. Overlapping PCR (polymer ase chain reaction) fragments covered the whole coding sequence as wel l as the 5' untranslated region of the 5-HT1A gene. The region upstrea m to the coding sequence we investigated contains a functional promote r. We found two rare nucleotide sequence variants. Both mutations are located in the coding region of the gene: a coding mutation (A-->G) in nucleotide position 82 which leads to an amino acid exchange (Ile-->V al) in position 28 of the receptor protein and a silent mutation (C--> T) in nucleotide position 549. The occurrence of the Ile-28-Val substi tution was studied in an extended sample of patients (n = 352) and con trols (n = 210) but was found in similar frequencies in all groups. Th us, this mutation is unlikely to play a significant role in the geneti c predisposition to the diseases investigated. In conclusion, our stud y does not provide evidence that the 5-HT1A gene plays either a major or a minor role in the genetic predisposition to schizophrenia, bipola r affective disorder, or Tourette's syndrome. (C) 1995 Wiley-Liss, Inc .