title: First example of an FY*01 allele associated with weakened expression of Fya on red blood cells.
abstract: Duffy antigens are important in immunohematology. the reference allele for the Duffy gene (FY) is FY*02, which encodes Fy(b). An A>G single nucleotide polymorphism (SNP) at coding nucleotide (c.) 125 in exon 2 defines the FY*01 allele, which encodes the antithetical Fy(a). A C>T SNP at c.265 in the FY*02 allele is associated with weakening of Fy(b) expression on red blood cells (R BCs) (called Fy(x)). until recently, this latter change had not been described on a FY*01 background allele. Phenotype-matched units were desired for a multi-transfused Vietnamese fetus with α-thalassemia. Genotyping of the fetus using a microarray assay that interrogates three SNPs (c.1-67, c.125, and c.265) in FY yielded indeterminate results for the predicted Duffy phenotype. Genomic sequencing of FY exon 2 showed that the fetal sample had one wild-type FY*01 allele and one new FY*01 allele with the c.265C>T SNP, which until recently had only been found on the FY*02 allele. Genotyping performed on samples from the proband's parents indicated that the father had the same FY genotype as the fetus. Flow cytometry, which has been previously demonstrated as a useful method to study antigen strength on cells, was used to determine if this new FY*01 allele was associated with reduced Fy(a) expression on the father's RBCs. Median fluorescence intensity of the father's RBCs (after incubation with anti-FY(a) and fluorescein-labeled anti-IgG) was similar to known FY*01 heterozygotes. and significantly weaker than known FY*01 homozygotes. In conclusion, the fetus and father both had one normal FY*01 allele and one new FY*01W.01, is associated with weakened expression of Fy(a) on RBCs.
authors.affiliation: MS, MT(ASCP)SBB (corresponding author), Lead Technologist, Special Immunohematology Laboratory, American Red Cross Blood Services, Southern California Region, 100 Red Cross Circle, Pomona, CA 91768.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Arndt
authors.affiliation: MS, MLT(ASCP)SBB, Laboratory Manager.
authors.forename: Trina
authors.initials: T
authors.lastname: Horn
authors.affiliation: MS, Laboratory Supervisor; Rochelle Young, Molecular Technologist I, American Red Cross National Molecular Laboratory, Philadelphia, PA.
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Keller
authors.affiliation: MT(ASCP)SBB, Manager, Quality, Compliance, and Regulatory Affairs, Children's Hospital Los Angeles, Los Angeles, CA.
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Heri
authors.affiliation: PhD, Director, American Red Cross National Molecular Laboratory, Philadelphia, PA.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Keller
mesh_terms: D000483:Alleles; D004375:Duffy Blood-Group System / Q000235:genetics*; D004912:Erythrocytes / Q000378:metabolism*; D005192:Family Health; D005315:Fetal Diseases / Q000097:blood*; D005434:Flow Cytometry; D005838:Genotype; D060005:Genotyping Techniques / Q000379:methods; D006801:Humans; D008297:Male; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D017085:alpha-Thalassemia / Q000097:blood*
chemical_list: D004375:Duffy Blood-Group System