title: New antigen in the Dombrock blood group system, DOYA, ablates expression of Do(a) and weakens expression of Hy, Jo(a), and Gy(a) antigens.
abstract: BACKGROUND
  The Dombrock (Do) blood group system consists of five distinct antigens: Do(a), Do(b), Gy(a), Hy, and Jo(a). Our finding of a patient whose plasma contained a Do-related alloantibody suggested the presence of a sixth antigen.
  
  
  METHODS
  Standard hemagglutination, flow cytometry, and polymerase chain reaction (PCR)-based methods were used throughout. Protein homology modeling was used to map the amino acid change on the protein structure.
  
  
  RESULTS
  The patient's red blood cells (RBCs) typed as Do(a-b-), Hy+(w), Jo(a+(w)), and Gy(a+(w)). The patient's plasma agglutinated RBCs with common Dombrock phenotypes. Reactivity with Hy- and Jo(a-) RBC samples was weak, and Gy(a-) RBC samples were nonreactive. DNA analysis showed the patient to be DO*793A (DO*A/DO*A), DO*323G, and DO*350C, which predicts the Do(a+b-), Hy+, and Jo(a+) phenotype, and revealed a homozygous single-nucleotide change of 547T>G in Exon 2 that is predicted to change tyrosine at Amino Acid Position 183 to aspartic acid. This missense substitution introduced a BtgZI restriction enzyme site. The sequence data were confirmed with a PCR-restriction fragment length polymorphism assay and revealed that the patient's parents and children were heterozygous DO*547T/G. Homology modeling predicted that the 183Tyr substitution by Asp altered the Cys182 environment and influenced the formation and/or stability of the Cys182-Cys231 disulfide bond.
  
  
  CONCLUSIONS
  The patient's DO genes have a single-nucleotide change, which leads to the absence of the high-prevalence antigen DOYA. The absence of this antigen is associated with 183Asp and silencing of Do(a) and weakening of Gy(a), Hy, and Jo(a) antigens.
authors.affiliation: Laboratory of Immunohematology, Institute for Transfusion Medicine, Charité-University Medicine, Berlin, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Mayer
authors.forename: Nicole
authors.initials: N
authors.lastname: Thornton
authors.forename: Salih
authors.initials: S
authors.lastname: Yürek
authors.forename: Dwane
authors.initials: D
authors.lastname: Wylie
authors.forename: Kim
authors.initials: K
authors.lastname: Hue-Roye
authors.forename: Joyce
authors.initials: J
authors.lastname: Poole
authors.forename: Thilo
authors.initials: T
authors.lastname: Bartolmäs
authors.forename: Abdulgabar
authors.initials: A
authors.lastname: Salama
authors.forename: Christine
authors.initials: C
authors.lastname: Lomas-Francis
authors.forename: Randall W
authors.initials: RW
authors.lastname: Velliquette
authors.forename: Karina
authors.initials: K
authors.lastname: Yazdanbakhsh
authors.forename: Marion E
authors.initials: ME
authors.lastname: Reid
mesh_terms: D036002:ADP Ribose Transferases / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D000328:Adult; D019943:Amino Acid Substitution; D001789:Blood Group Antigens / Q000096:biosynthesis* / Q000235:genetics; D004220:Disulfides / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006182:H-Y Antigen / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D006720:Homozygote; D006801:Humans; D007518:Isoantibodies / Q000737:chemistry / Q000276:immunology; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000276:immunology; D020125:Mutation, Missense; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics / Q000276:immunology
chemical_list: D001789:Blood Group Antigens; D004220:Disulfides; D006182:H-Y Antigen; D007518:Isoantibodies; D008565:Membrane Proteins; D036002:ADP Ribose Transferases; C105234:ART4 protein, human