P¹/P² genotyping of known and novel null alleles in the P1PK and GLOB histo‐blood group systems

Abstract

For the first time, p alleles were shown to occur on both P(1) and P(2) allelic backgrounds. Furthermore, P(1) /P(2) genotyping predicted the P1 (k) versus P2 (k) phenotype in more than 90% of globoside-deficient samples. The number of GLOB-null alleles was increased by 50% and several P1PK-null alleles were identified.

Identification of the Molecular and Genetic Basis of PX2, a Glycosphingolipid Blood Group Antigen Lacking on Globoside-deficient Erythrocytes

“…Transcript levels of B3GALNT1 were also significantly decreased in the cells co-transfected with B3GALNT1 ORF and B3GALNT1 siRNA as compared with the B3GALNT1 ORF-and negative control siRNA-or GAPDH siRNAtransfected cells, respectively (data not shown). This shows that the enzyme encoded by B3GALNT1 is capable of PX2 antigen synthesis in MEG-01 cells in addition to synthesizing the P antigen as shown previously (35). This glycosyltransferase can thereby use two different acceptor substrates, neolactotetraosylceramide (paragloboside) or Gb3 (P k ) to form either a neolacto or a globo series glycosphingolipid.…”

“…P antigen is believed to be the main product of the glycosyltransferase encoded by B3GALNT1, although this enzyme is now also shown to be capable of PX2 antigen synthesis. However, to be able to induce a high P antigen expression in MEG-01 cells, double transfection with A4GALT was needed as reported previously (35) to enhance the expression of its precursor, P k . One may therefore conclude from these observations that A4GALT appears to be a limiting step component of lactosylceramide elongation, and if the enzyme expression is low, it directs its enzymatic attention elsewhere (45), e.g.…”

“…Four different B3GALNT1 constructs were made, including a consensus allele (B3GALNT1 open reading frame (ORF)) and three known naturally occurring mutants, 202C3 T (R68stop), 376G3 A (D126N) and 449A3 G (D150G), as described previously (35). The 202C3 T and 449A3 G mutants are null alleles because they were identified in samples of the P k phenotype.…”

Human Genetic Determinants of Viral Diseases

“…Likewise, cells from P-negative donors could not be infected, even at extreme doses (15). To date, P-negative phenotypes have been attributed to several rare polymorphisms in two genes, B3GALNT1 and A4GALT, which encode glycosyltransferases involved in distinct steps of P antigen biosynthesis (48, 138, 165, 166). …”

The differential expression of the blood group P1‐A4GALT and P2‐A4GALT alleles is stimulated by the transcription factor early growth response 1

“…The molecular genetic bases that lead to different P k and NOR blood group phenotypes have been revealed. It is known that mutations in the coding region of the A4GALT gene leading to a nonfunctional α4GalT enzyme result in the rare p blood group phenotype . Individuals with such a mutation lack both the P1 and the P k antigens on their RBCs, as well as the globoside series of antigens that are downstream to P k .…”