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Two previously proposed P1/P2-differentiating and nine novel polymorphisms at the A4GALT (Pk) locus do not correlate with the presence of the P1 blood group antigen.

ABSTRACT: BACKGROUND: The molecular genetics of the P blood group system and the absence of P1 antigen in the p phenotype are still enigmatic. One theory proposes that the same gene encodes for both the P1 and Pk glycosyltransferases, but no polymorphisms in the coding region of the Pk gene explain the P1/P2 phenotypes. We investigated the potential regulatory regions up- and downstream of the A4GALT (Pk) gene exons. RESULTS: P1 (n = 18) and P2 (n = 9) samples from donors of mainly Swedish descent were analysed by direct sequencing of PCR-amplified 5'- and 3'-fragments surrounding the Pk coding region. Seventy-eight P1 and P2 samples were investigated with PCR using allele-specific primers (ASP) for two polymorphisms previously proposed as P2-related genetic markers (-551_-550insC, -160A>G). Haplotype analysis of single nucleotide polymorphisms was also performed with PCR-ASP. In approximately 1.5 kbp of the 3'-untranslated region one new insertion and four new substitutions compared to a GenBank sequence (AL049757) were found. In addition to the polymorphisms at positions -550 and -160, one insertion, two deletions and one substitution were found in approximately 1.0 kbp of the 5'-upstream region. All 20 P2 samples investigated with PCR-ASP were homozygous for -550insC. However, so were 18 of the 58 P1 samples investigated. Both the 20 P2 and the 18 P1 samples were also homozygous for -160G. CONCLUSION: The proposed P2-specific polymorphisms, -551_-550insC and -160G, found in P2 samples in a Japanese study were found here in homozygous form in both P1 and P2 donors. Since P2 is the null allele in the P blood group system it is difficult to envision how these mutations would cause the P2 phenotype. None of the novel polymorphisms reported in this study correlated with P1/P2 status and the P1/p mystery remains unsolved.

SUBMITTER: Hellberg A

PROVIDER: S-EPMC1282566 | biostudies-literature | 2005

REPOSITORIES: biostudies-literature

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Two previously proposed P1/P2-differentiating and nine novel polymorphisms at the A4GALT (Pk) locus do not correlate with the presence of the P1 blood group antigen.

Hellberg Asa A Chester M Alan MA Olsson Martin L ML

BMC genetics 20051007

<h4>Background</h4>The molecular genetics of the P blood group system and the absence of P1 antigen in the p phenotype are still enigmatic. One theory proposes that the same gene encodes for both the P1 and Pk glycosyltransferases, but no polymorphisms in the coding region of the Pk gene explain the P1/P2 phenotypes. We investigated the potential regulatory regions up- and downstream of the A4GALT (Pk) gene exons.<h4>Results</h4>P1 (n = 18) and P2 (n = 9) samples from donors of mainly Swedish de ...[more]

PMID: 16212661

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Project description:Malaria remains one the most infectious and destructive protozoan diseases worldwide. Plasmodium falciparum, a protozoan parasite with a complex life cycle and high genetic variability responsible for the difficulties in vaccine development, is implicated in most malaria-related deaths. In the course of study, we prepared a set of antigens based on P-proteins from P. falciparum and determined their immunogenicity in an in vivo assay on a mouse model. The pentameric complex P0-(P1-P2)2 was prepared along with individual P1, P2, and P0 antigens. We determined the level of cellular- and humoral-type immunological response followed by development of specific immunological memory. We have shown that the number of Tc cells increased significantly after the first immunization with P2 and after the second immunization with P1 and P0-(P1-P2)2, which highly correlated with the number of Th1 cells. P0 appeared as a poor inducer of cellular response. After the third boost with P1, P2, or P0-(P1-P2)2, the initially high cellular response dropped to the control level accompanied by elevation of the number of activated Treg cells and a high level of suppressive TGF-β. Subsequently, the humoral response against the examined antigens was activated. Although the titers of specific IgG were increasing during the course of immunization for all antigens used, P2 and P0-(P1-P2)2 were found to be significantly stronger than P1 and P0. A positive correlation between the Th2 cell abundance and the level of IL-10 was observed exclusively after immunization with P0-(P1-P2)2. An in vitro exposure of spleen lymphocytes from the immunized mice especially to the P1, P2, and P0-(P1-P2)2 protein caused 2-3-fold higher cell proliferation than that in the case of lymphocytes from the nonimmunized animals, suggesting development of immune memory. Our results demonstrate for the first time that the native-like P-protein pentameric complex represents much stronger immune potential than individual P-antigens.

Dataset Information

Two previously proposed P1/P2-differentiating and nine novel polymorphisms at the A4GALT (Pk) locus do not correlate with the presence of the P1 blood group antigen.

Publications

Two previously proposed P1/P2-differentiating and nine novel polymorphisms at the A4GALT (Pk) locus do not correlate with the presence of the P1 blood group antigen.

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