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.
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.
Mayer
Beate
B
Laboratory of Immunohematology, Institute for Transfusion Medicine, Charité-University Medicine, Berlin, Germany.
Thornton
Nicole
N
Yürek
Salih
S
Wylie
Dwane
D
Hue-Roye
Kim
K
Poole
Joyce
J
Bartolmäs
Thilo
T
Salama
Abdulgabar
A
Lomas-Francis
Christine
C
Velliquette
Randall W
RW
Yazdanbakhsh
Karina
K
Reid
Marion E
ME
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
D001789:Blood Group Antigens; D004220:Disulfides; D006182:H-Y Antigen; D007518:Isoantibodies; D008565:Membrane Proteins; D036002:ADP Ribose Transferases; C105234:ART4 protein, human