title: A novel mutation in the coding sequence of the FY*B allele of the Duffy chemokine receptor gene is associated with an altered erythrocyte phenotype.
abstract: The Duffy blood group system is of clinical and biological significance. Antibodies to Duffy antigens are responsible for some cases of transfusion incompatibility and newborn hemolytic disease. The Duffy protein is a receptor for the Plasmodium vivax erythrocyte-binding protein and is also a receptor for various chemokines (thus renamed Duffy Antigen Receptor for Chemokines [DARC]). The two Duffy polymorphic antigens, Fya and Fyb (coded by the FY*A and FY*B alleles), are present on erythrocyte membranes. The Fy(a-b-) phenotype is the predominant one in populations of black people and also occurs in other populations, including some non-Ashkenazi Jewish groups. The Fy(a-b-) phenotype has been associated with a mutation in the FY*B promoter at the GATA box that abolishes the expression of erythrocyte Duffy protein. We describe here a novel mutation, present in the FY*B coding sequence (271C --> T), that is associated with some Fy(b-) phenotypes among non-Ashkenazi Jews and among Brazilian blacks. The mutation is present in Fy(b-) individuals, who have wild-type FY*B GATA and carry the previously described 304G --> A substitution. The 271C --> T and 304G --> A can be identified by restriction enzyme-generated restriction fragment length polymorphisms. The 271C --> T substitution represents a considerable change in chemical nature (Arg91 --> Cys), one which may affect the antigenic determinants of DARC, and thus be of clinical significance. The mutation may have implications for some physiological roles of DARC and be of interest in malaria research and in studies of population genetics.
authors.affiliation: Department of Human Genetics, Sackler School of Medicine, Tel-Aviv University, Tel Aviv, Israel.
authors.forename: N
authors.initials: N
authors.lastname: Parasol
authors.forename: M
authors.initials: M
authors.lastname: Reid
authors.forename: M
authors.initials: M
authors.lastname: Rios
authors.forename: L
authors.initials: L
authors.lastname: Castilho
authors.forename: I
authors.initials: I
authors.lastname: Harari
authors.forename: N S
authors.initials: NS
authors.lastname: Kosower
mesh_terms: D000372:Agglutination Tests; D000483:Alleles; D000818:Animals; D000953:Antigens, Protozoan; D001665:Binding Sites; D044383:Black People / Q000235:genetics*; D001938:Brazil; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D004198:Disease Susceptibility; D004375:Duffy Blood-Group System / Q000235:genetics*; D004910:Erythrocyte Membrane / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D050981:Erythroid-Specific DNA-Binding Factors; D005786:Gene Expression Regulation; D005787:Gene Frequency; D006801:Humans; D007585:Jews / Q000235:genetics*; D016780:Malaria, Vivax / Q000208:ethnology / Q000235:genetics; D010641:Phenotype; D010966:Plasmodium vivax / Q000378:metabolism; D017354:Point Mutation; D012150:Polymorphism, Restriction Fragment Length; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: C473745:ACKR1 protein, human; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D050981:Erythroid-Specific DNA-Binding Factors; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D014157:Transcription Factors