Linked Life Data

20971946

Source:http://linkedlifedata.com/resource/pubmed/id/20971946

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-14
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1528-0020
pubmed:author
pubmed:issnType
Electronic
pubmed:day
13
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
678-87
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
pubmed:year
2011
pubmed:articleTitle
Identification of a novel A4GALT exon reveals the genetic basis of the P1/P2 histo-blood groups.
pubmed:affiliation
Department of Clinical Immunology and Transfusion Medicine, University and Regional Laboratories, Lund, Sweden.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't