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Insights into the Holley- and Joseph- phenotypes
Maria Rios1, Kim Hue-Roye, Ragnhild Øyen
1Immunochemistry Laboratory, New York Blood Center, New York, New York 10021, USA.
Background:
The Dombrock blood group system consists of two antithetical antigens (Do(a) and Do(b)) and three high-incidence antigens (Gregory [Gy(a)], Holley [Hy], and Joseph [Jo(a)]). Hy and Jo(a) have an unusual phenotypic relationship. All Hy- RBCs are Jo(a-), but not all Jo(a-) RBCs are Hy-. The molecular background associated with Hy- and Jo(a-) phenotypes is reported.
Study Design And Methods:
DNA from 18 probands with Gy(a+(w)) Hy- Jo(a-) RBCs (Hy- phenotype) and from 13 probands with Gy(a+) Hy+(w) Jo(a-) RBCs (Jo[a-] phenotype) was tested.
Results:
Sequencing and PCR-RFLP revealed 323 G>T (Gly 108Val) and 378 T>C (silent mutation) changes on a DOB background (HY) associated with the Hy- samples. The sister of the original Hy- proband and the majority of samples had an additional mutation of 898 C>G (Leu300Val) (HY1); others had 898C (300Leu) (HY2). In the Jo(a-) phenotype, there is a 350 C>T (Thr1 17Ile) and a 378 C>T (silent mutation) change on a DOA background (JO).
Conclusion:
The results provide an explanation for the variation in typing results in antibody producers. The ablation of Jo(a) in the Hy- phenotype and the weakening of Hy in the Jo(a-) phenotype may be due to the close proximity of these antigens. The 898 C>G mutation, within the sequence motif for glycosylphosphatidylinositol linkage, may cause reduced efficiency of anchoring the protein to the RBC membrane, thereby weakening the expression of Gy(a) and Do(b).