Sequence Variation of Human Platelet Membrane Glycoprotein IIIa Associated with the Yuka/Yukb Alloantigen System.

Abstract
The human platelet alloantigens play a prominent role in provoking neonatal alloimmune thrombocytopenic purpura. The frequencies of Yuka and Yukb antigens are 1.7% and 99.9% in the Japanese population, respectively. The Yuk alloantigen system is localized on the human platelet membrane glycoprotein (GP)IIIa. To investigate the molecular structure of Yuk alloantigenic determinants, we amplified GP IIIa cDNAs from Yuka/a and Yukb/b homozygous individuals. A single nucleotide substitution was found at base 526 of GP IIIa cDNA by direct DNA sequencing analysis. The Yukb/b homozygous individuals bore G at this position while the Yuka/a had A. This base change results in the substitution of glutamine in Yuka for arginine in Yukb at amino acid residue 143 of glycoprotein IIIa molecule. Slot blotting analysis using sequence-specific oligonucleotide probes demonstrated that this Arg/Gln polymorphism is associated with the Yuk alloantigen system.

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