Disruption of a GATA motif in the Duffy gene promoter abolishes erythroid gene expression in Duffy–negative individuals

Abstract

The mRNA for the Duffy blood group antigen, the erythrocyte receptor for the Plasmodium vivax malaria parasite, has recently been cloned and shown to encode a widely expressed chemokine receptor. Here, we show that the Duffy antigen/chemokine receptor gene (DARC) is composed of a single exon and that most Duffy–negative blacks carry a silent FY^*B allele with a single T to C substitution at nucleotide −46. This mutation impairs the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor. With the recent characterization of the FY^*A and FY^*B alleles, these findings provide the molecular basis of the Duffy blood group system and an explanation for the erythroid–speeific repression of the DARC gene in Duffy–negative individuals.