The Duffy blood group system, which consists of 4 alleles, 5 phenotypes, and 5 antigens, is important in clinical medicine because of transfusion incompatibilities and hemolytic disease of the newborn. Duffy antigens are located on DARC (613665), an ... The Duffy blood group system, which consists of 4 alleles, 5 phenotypes, and 5 antigens, is important in clinical medicine because of transfusion incompatibilities and hemolytic disease of the newborn. Duffy antigens are located on DARC (613665), an acidic glycoprotein found on erythrocytes and other cells throughout the body. The 2 principal antigens, Fy(a) and Fy(b), are produced by the FYA and FYB codominant alleles (see 613665.0001). Four phenotypes are defined by the corresponding antibodies, anti-Fy(a) and anti-Fy(b): Fy(a+b-), Fy(a-b+), Fy(a+b+), and Fy(a-b-). Fy(a-b-), or Duffy null, is the major phenotype in African and American blacks and is characterized by the presence of Fy(b) on nonerythroid cells, but an absence of Fy(b) on erythrocytes. The Fy(a-b-) phenotype is associated with complete resistance to infection by the malarial parasite Plasmodium vivax (see 611162). Individuals with the Fy(a-b-) phenotype have the FYB-erythroid silent (FYB-ES) allele with a mutation in the DARC promoter (613665.0002). A fifth phenotype, Fy(bwk), or Fy(x), is characterized by weak Fy(b) expression on erythrocytes due to a reduced amount of protein. Individuals with the Fy(bwk) phenotype have the FYB-weak (FYB-WK) allele, also called the FYX allele, with a missense mutation in DARC (613665.0003). Other Duffy antigens include Fy3, Fy4, Fy5, and Fy6 (reviews by Pogo and Chaudhuri (2000), Langhi and Bordin (2006), and Meny (2010)).
An association between sickle cell trait (603903) and Duffy-null blood group was demonstrated in Saudi Arabs (Gelpi and King, 1976). Neither linkage nor association of the usual type was the basis, but rather a protection against malaria provided ... An association between sickle cell trait (603903) and Duffy-null blood group was demonstrated in Saudi Arabs (Gelpi and King, 1976). Neither linkage nor association of the usual type was the basis, but rather a protection against malaria provided by both traits.
Tournamille et al. (1995) found that a single amino acid difference (G42D; 613665.001) in DARC accounts for the difference between the FYA and FYB alleles at the Duffy blood group locus. Mallinson et ... - FYA/FYB Polymorphism Tournamille et al. (1995) found that a single amino acid difference (G42D; 613665.001) in DARC accounts for the difference between the FYA and FYB alleles at the Duffy blood group locus. Mallinson et al. (1995) also reported the basis for the FYA/FYB polymorphism. For further information on the FYA/FYB polymorphism, see MOLECULAR GENETICS in 613665. - Fy(a-b-) Phenotype The Fy(a-b-) phenotype is rare among white and Asian populations, whereas it is the predominant phenotype among populations of black people, especially those originating in West Africa. Tournamille et al. (1995) demonstrated that the molecular basis of the Fy(a-b-) phenotype is a point mutation, -67T-C (613665.0002), in a consensus binding site for GATA1 (305371), a transcription factor active in erythroid cells. The Fy(a-b-) phenotype provides complete protection from Plasmodium vivax infection (see 611162). Mallinson et al. (1995) presented evidence for 2 different genetic backgrounds giving rise to the Fy(a-b-) phenotype. The Duffy gene from a very rare Caucasian individual (AZ) with the Fy(a-b-) phenotype had a 14-bp deletion (613665.0004) that resulted in a frameshift that introduced a stop codon and produced a putative truncated DARC protein. The only known examples of the Fy(a-b-) phenotype in Caucasians were AZ and Czech gypsies. For further information on the molecular genetics underlying the Fy(a-b-) phenotype, see MOLECULAR GENETICS in 613665. - Fy(bwk) Phenotype Tournamille et al. (1998) and Olsson et al. (1998) described a Duffy allele, FYB-WK, or FYX, in approximately 3.5% of the population that, because of an arg89-to-cys (R89C; 613665.0003) substitution in the first cytoplasmic domain of DARC, results in reduced levels of protein, lower antigen expression, and reduced ability to bind chemokines. The phenotype is called Fy(bwk), Fy(x), or either Fy(a-b+(weak)) or Fy(a+b+(weak)) For further information on the molecular genetics underlying the Fy(bwk) phenotype, see MOLECULAR GENETICS in 613665.