Insights into the Holley- and Joseph- phenotypes.

Area of Science:

• Hematology
• Genetics
• Immunology

Background:

• The Dombrock blood group system includes Do(a), Do(b), Gy(a), Hy, and Jo(a) antigens.
• Hy and Jo(a) exhibit an unusual phenotypic relationship where all Hy- red blood cells (RBCs) are Jo(a-), but not vice versa.

Purpose of the Study:

• To investigate the molecular basis of the Hy- and Jo(a-) phenotypes within the Dombrock blood group system.
• To explain variations in typing results observed in antibody producers.

Main Methods:

• DNA analysis using sequencing and PCR-RFLP was performed on 18 Hy- and 13 Jo(a-) phenotype probands.
• Genetic mutations associated with specific Dombrock phenotypes were identified.

Main Results:

• Hy- phenotype RBCs showed 323 G>T and 378 T>C mutations on a DOB background, with additional 898 C>G (HY1) or 898C (HY2) mutations observed.
• Jo(a-) phenotype RBCs exhibited 350 C>T and 378 C>T mutations on a DOA background.

Conclusions:

• The identified mutations provide a molecular explanation for the Hy- and Jo(a-) phenotypes.
• The close proximity of Hy and Jo(a) antigens may lead to the ablation of Jo(a) in Hy- and weakening of Hy in Jo(a-) phenotypes.
• The 898 C>G mutation may impair glycosylphosphatidylinositol anchoring, affecting Gy(a) and Do(b) expression.