The coding sequence of Duffy blood group gene in humans and simians: restriction fragment length polymorphism, antibody and malarial parasite specificities, and expression in nonerythroid tissues in Duffy- negative individuals

Abstract

The coding and untranslated flanking sequences of Duffy gene (FY) in humans and simians are in a single exon. The difference between the two codominant alleles, FY*A and FY*B, is a single change at nucleotide 306: guanidine is in FY*A and adenine is in FY*B. This produces a codon change that subsequently modifies the amino acid at position 43 of gpFy, the major subunit of the Duffy blood group protein complex. The glycine at this position in antigen Fya exchanges with aspartic acid in antigen Fyb. The guanidine at nucleotide 306 creates an additional Ban I restriction site in FY*A. Ban I digestion of DNA-PCR amplified products of FY*B and FY*A yields three and four fragments, respectively. Restriction fragment length polymorphism (RFLP) studies show that Fy(a+b-) and Fy(a-b+) whites are FY homozygous, that most Fy(a-b-) blacks have FY*B, and most Fy(a+b-) blacks are FY*A/FY*B heterozygous. In the black population a silent FY*B is very common, but a silent FY*A has not been found yet. On RNA blot analysis, the gpFy cDNA clone detected mRNA in the lung, spleen, and colon but not in the bone marrow of Duffy-negative individuals. Therefore, there is no null phenotype in Fy(a-b-) blacks. The gpFy homology between human and chimpanzee is 99% with a single residue change at position 116 (valine to isoleucine), whereas a 94% homology is found in squirrel and rhesus monkeys, and there is a 93% homology in aotus monkey when compared with humans. The N-terminal exocellular domain of simian gpFy helps to identify a set of amino acids critical for antibody and malarial parasite specificities.

International Union of Basic and Clinical Pharmacology. LXXXIX. Update on the Extended Family of Chemokine Receptors and Introducing a New Nomenclature for Atypical Chemokine Receptors

“…The two antithetical Duffy erythrocyte antigens, Fy a and Fy b , are the products of two polymorphic alleles FYA and FYB present on chromosome 1. They differ only in a single nucleotide, G versus A within codon 42, encoding glycine and aspartic acid in Fy a and Fy b , respectively (Chaudhuri et al, 1995;Iwamoto et al, 1995). ACKR1's extracellular N-terminal domain, which bears the blood group determinants, is linked with the fourth extracellular 46 Bachelerie et al domain via a disulfide bond.…”

The value of DNA analysis for antigens in the Duffy blood group system

“…The Duffy glycoprotein, also known as the Duffy antigen receptor for chemokines, is expressed in erythroid and nonerythroid cells, including the endothelium, brain, colon, lung, spleen, kidney, thyroid, and thymus, and plays a role in inflammation and malaria infection. 3 It is a member of the superfamily of chemokine receptors 4,5 and the receptor for the human malarial parasite, Plasmodium vivax, and the simian malarial parasite, Plasmodium knowlesi. 5,6 The parasitespecific binding site, the binding site for chemokines, and the major antigenic domains are located in overlapping regions at the exocellular N-terminal terminus.…”

Insights into the Structure and Function of Membrane Polypeptides Carrying Blood Group Antigens

“…The frequency, the structure and expression of the FY*Fy allele, responsible for the Fy(a-b-) red cell phenotype, differ according to the populations investigated. In blacks, Fy(a-b-) is conveyed by homozygosity for a so called "bone marrow silent FY*B allele" [203] which differ from a normal FY*B allele by a T-46C mutation in the promoter region [204] (Figure 8). By disrupting a binding site for h-GATA-1 erythroid transcription factor, this mutation specifically abolishes the transcriptional activity of the FY promoter in erythroid cells.…”