EVOLUTION OF HAPLOTYPES AT THE DRD2 LOCUS

We present here the first evolutionary perspective on haplotypes at DR D2, the locus for the dopamine D-2 receptor. The dopamine D-2 receptor plays a critical role in the functioning of many neural circuits in t he human brain. If functionally relevant variation at the DRD2 locus e xists, understanding the evolution of haplotypes on the basis of polym orphic sites encompassing the gene should provide a powerful framework for identifying that variation. Three DRD2 polymorphisms (TaqI ''A'' and ''B'' RFLPs and the (CA)(n) short tandem repeat polymorphism) enco mpassing the coding sequences have been studied in 15 populations; the se markers are polymorphic in all the populations studied, and they di splay strong and significant linkage disequilibria with each other. Th e common haplotypes for the two TaqI RFLPs are separately derived from the ancestral haplotype but predate the spread of modern humans aroun d the world. The knowledge of how the various haplotypes have evolved, the allele frequencies of the haplotypes in human populations, and th e physical relationships of the polymorphisms to each other and to the functional parts of the gene should now allow proper design and inter pretation of association studies.