title: Insights into the Holley- and Joseph- phenotypes.
abstract: 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.
  
  
  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).
  
  
  CONCLUSIONS
  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).
authors.affiliation: Immunochemistry Laboratory, New York Blood Center, New York, New York 10021, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Rios
authors.forename: Kim
authors.initials: K
authors.lastname: Hue-Roye
authors.forename: Ragnhild
authors.initials: R
authors.lastname: Øyen
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Miller
authors.forename: Marion E
authors.initials: ME
authors.lastname: Reid
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D044383:Black People / Q000235:genetics; D001789:Blood Group Antigens / Q000235:genetics*; D001788:Blood Grouping and Crossmatching; D004252:DNA Mutational Analysis; D017261:Glycosylphosphatidylinositols / Q000097:blood; D006801:Humans; D008969:Molecular Sequence Data; D002679:Pan troglodytes / Q000235:genetics / Q000276:immunology; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D044465:White People / Q000235:genetics
chemical_list: D001789:Blood Group Antigens; D017261:Glycosylphosphatidylinositols