IDENTIFICATION OF GENETIC-VARIATION IN THE HUMAN SEROTONIN 1D-BETA RECEPTOR GENE

Disturbances of serotonergic pathways have been implicated in a wide v ariety of neuropsychiatric disorders such as depression, anxiety, migr aine, and substance abuse. Genetic variation in genes coding for serot onin receptor proteins might well be involved in the genetic predispos ition to these diseases and/or of pharmacogenetic relevance. Genomic s amples from 46 unrelated healthy subjects were investigated by single- strand conformation analysis (SSCA) to screen for genetic variation in the human serotonin 1D beta (5-HT1D beta) receptor gene. Overlapping PCR (polymerase chain reaction) fragments covered the whole coding seq uence as well as 5' untranslated regions of the 5-HT1D beta gene. Four nucleotide sequence variants were found: a coding mutation in nucleot ide position 371 which leads to an amino acid exchange (Phe-->Cys) in position 124 of the receptor protein and three mutations in the 5' fla nking region. For all mutations specific PCR-based assays were develop ed which allow rapid genotyping in populations and families. To our kn owledge, the Phe-124-Cys substitution is the first natural occurring m olecular variant which has been identified for the 5-HT1D beta recepto r so far. (C) 1994 Academic Press.