ALLELES AT THE DOPAMINE D-4 RECEPTOR LOCUS DO NOT CONTRIBUTE TO THE GENETIC SUSCEPTIBILITY TO SCHIZOPHRENIA IN A LARGE SWEDISH KINDRED

The discovery of a functional polymorphism within the dopamine D-4 rec eptor gene (DRD4) has not only strengthened the hypotheses implicating DRD4 in the etiology of neuropyschiatric disorders, but also provided a genetic marker for testing these hypotheses. The possibility of the dopamine D-4 receptor as a candidate gene for schizophrenia was inves tigated in a large Swedish kindred segregating for schizophrenia. Link age to schizophrenia was tested by linkage analyses of 6 polymorphic m arkers (at 4 loci) in chromosome 11p15.5 including the dopamine D-4 re ceptor (DRD4) and the tyrosine hydroxylase (TH) loci. Schizophrenia wa s excluded from close linkage to the DRD4 locus using two of the polym orphisms located within the dopamine D-4 receptor gene. The first DRD4 polymorphism consists of variation in the number of a 48 bp imperfect direct repeat in the third exon; the second consists of a variable nu mber of repeated G nucleotides in the first intron. In addition, some of the individuals homozygous for four or seven copies of 48 bp repeat alleles were tested for previously reported sequence variation among repeats. No single haplotype of the DRD4 alleles or haplotype of other markers in chromosome l1p15.5 was found to be common to the schizophr enic individuals in this family. Therefore, we find no evidence for li nkage of the Dq receptor, or this region of 11p15.5, with genetic susc eptibility to schizophrenia in this kindred. (C) 1993 Wiley-Liss, Inc.