Source:http://linkedlifedata.com/resource/pubmed/id/20971946
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
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pubmed:dateCreated |
2011-1-14
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pubmed:abstractText |
The A4GALT locus encodes a glycosyltransferase that synthesizes the terminal Gal?1-4Gal of the P(k) (Gb3/CD77) glycosphingolipid, important in transfusion medicine, obstetrics, and pathogen susceptibility. Critical nucleotide changes in A4GALT not only abolish P(k) formation but also another Gal?1-4Gal-defined antigen, P1, which belongs to the only blood group system for which the responsible locus remains undefined. Since known A4GALT polymorphisms do not explain the P1-P(k)+ phenotype, P(2), we set out to elucidate the genetic basis of P(1)/P(2). Despite marked differences (P(1) > P(2)) in A4GALT transcript levels in blood, luciferase experiments showed no difference between P(1)/P(2)-related promoter sequences. Investigation of A4GALT mRNA in cultured human bone marrow cells revealed novel transcripts containing only the noncoding exon 1 and a sequence (here termed exon 2a) from intron 1. These 5'-capped transcripts include poly-A tails and 3 polymorphic sites, one of which was P(1)/P(2)-specific among > 200 donors and opens a short reading frame in P(2) alleles. We exploited these data to devise the first genotyping assays to predict P1 status. P(1)/P(2) genotypes correlated with both transcript levels and P1/P(k) expression on red cells. Thus, P(1) zygosity partially explains the well-known interindividual variation in P1 strength. Future investigations need to focus on regulatory mechanisms underlying P1 synthesis.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Globosides,
http://linkedlifedata.com/resource/pubmed/chemical/P Blood-Group System,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Isoforms,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/galactopyranosyl-1-4-paragloboside
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1528-0020
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pubmed:author | |
pubmed:issnType |
Electronic
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pubmed:day |
13
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pubmed:volume |
117
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
678-87
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pubmed:meshHeading |
pubmed-meshheading:20971946-Alternative Splicing,
pubmed-meshheading:20971946-Bone Marrow Cells,
pubmed-meshheading:20971946-Cell Separation,
pubmed-meshheading:20971946-Exons,
pubmed-meshheading:20971946-Flow Cytometry,
pubmed-meshheading:20971946-Genotype,
pubmed-meshheading:20971946-Globosides,
pubmed-meshheading:20971946-Humans,
pubmed-meshheading:20971946-Molecular Sequence Data,
pubmed-meshheading:20971946-P Blood-Group System,
pubmed-meshheading:20971946-Phenotype,
pubmed-meshheading:20971946-Polymorphism, Restriction Fragment Length,
pubmed-meshheading:20971946-Polymorphism, Single Nucleotide,
pubmed-meshheading:20971946-Promoter Regions, Genetic,
pubmed-meshheading:20971946-Protein Isoforms,
pubmed-meshheading:20971946-RNA, Messenger,
pubmed-meshheading:20971946-Reverse Transcriptase Polymerase Chain Reaction
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pubmed:year |
2011
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pubmed:articleTitle |
Identification of a novel A4GALT exon reveals the genetic basis of the P1/P2 histo-blood groups.
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pubmed:affiliation |
Department of Clinical Immunology and Transfusion Medicine, University and Regional Laboratories, Lund, Sweden.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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