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Blood, 1 March 2002, Vol. 99, No. 5, pp. 1692-1698
IMMUNOBIOLOGY
A tyrosine703serine polymorphism of CD109 defines the Gov
platelet alloantigens
Andre C. Schuh,
Nick A. Watkins,
Quang Nguyen,
Nicholas J. Harmer,
Martin Lin,
Joseph Y. A. Prosper,
Kate Campbell,
D. Robert Sutherland,
Paul Metcalfe,
Wendy Horsfall, and
Willem H. Ouwehand
From the Institute of Medical Science and the
Departments of Medicine, Medical Biophysics, and Immunology, University
of Toronto, and the Division of Hematology/Medical Oncology, The
Princess Margaret Hospital, Toronto, ON, Canada; the Division of
Transfusion Medicine, Department of Hematology, University of Cambridge
and National Blood Service-East Anglia, Cambridge, United Kingdom; and
the National Institute for Biological Standards and Control, Potters
Bar, United Kingdom.
The biallelic platelet-specific Gov antigen system implicated in
refractoriness to platelet transfusion, neonatal alloimmune thrombocytopenia, and posttransfusion purpurais carried by the glycosylphosphatidylinositol (GPI)-linked protein CD109. The recent identification of the human CD109 complementary DNA (cDNA) has allowed
the molecular nature of the Gov alleles to be elucidated. By using
reverse transcriptase-polymerase chain reaction (RT-PCR) to amplify
CD109 cDNAs from 6 phenotypically homozygous Govaa and
Govbb individuals, we have determined that the Gov alleles
differ by an A to C single nucleotide polymorphism (SNP) at position
2108 of the coding region, resulting in a Tyr/Ser substitution at CD109 amino acid 703. Allele-specific PCR sequence-specific primers (SSP), PCR-restriction fragment length polymorphism, and
real-time PCR studies of 15 additional donors (5 Govaa, 5 Govbb, and 5 Govab) confirmed that this SNP
correlates with the Gov phenotype. In addition, Chinese hamster ovary
cells transiently expressing nucleotide 2108 A>C CD109 cDNA variants
were recognized specifically by allele-specific Gov antisera,
indicating that this polymorphism defines the Gov alloantigenic
determinants. Real-time PCR was then used to genotype 85 additional Gov
phenotyped donors. In all but 3 cases, genomic testing concurred with
the Gov phenotype. Repeat testing corrected 2 of these discrepancies in
favor of the genotyping result. The third discrepancy could not be
resolved, likely reflecting low-level CD109 expression below the
sensitivity of the phenotyping assay. We conclude that the Gov alleles
are defined by a 2108 A>C SNP that results in a Tyr703Ser substitution
of CD109 and that genotyping studies are more accurate for Gov
alloantigen determination than are conventional serologic methods.
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