Identification of a novel A4GALT exon reveals the genetic basis of the P1/P2 histo-blood groups.
Thuresson, Britt LU ; Westman, Julia LU and Olsson, Martin L LU
(2011)
In Blood
117(2).
p.678-687
- Abstract
- The A4GALT locus encodes a glycosyltransferase that synthesizes the terminal Galα1-4Gal 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 Galα1-4Gal-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... (More)
- The A4GALT locus encodes a glycosyltransferase that synthesizes the terminal Galα1-4Gal 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 Galα1-4Gal-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 non-coding 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/1710811
- author
- Thuresson, Britt
LU
; Westman, Julia
LU
and Olsson, Martin L
LU
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Blood
- volume
- 117
- issue
- 2
- pages
- 678 - 687
- publisher
- American Society of Hematology
- external identifiers
-
- wos:000286178700039
- pmid:20971946
- scopus:78751555877
- pmid:20971946
- ISSN
- 1528-0020
- DOI
- 10.1182/blood-2010-08-301333
- language
- English
- LU publication?
- yes
- id
- 19f6ba2e-125c-4696-bbf5-f91d93a768cd (old id 1710811)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/20971946?dopt=Abstract
- date added to LUP
- 2016-04-01 10:11:13
- date last changed
- 2024-01-06 10:04:02
@article{19f6ba2e-125c-4696-bbf5-f91d93a768cd,
abstract = {{The A4GALT locus encodes a glycosyltransferase that synthesizes the terminal Galα1-4Gal 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 Galα1-4Gal-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 non-coding 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.}},
author = {{Thuresson, Britt and Westman, Julia and Olsson, Martin L}},
issn = {{1528-0020}},
language = {{eng}},
number = {{2}},
pages = {{678--687}},
publisher = {{American Society of Hematology}},
series = {{Blood}},
title = {{Identification of a novel A4GALT exon reveals the genetic basis of the P1/P2 histo-blood groups.}},
url = {{http://dx.doi.org/10.1182/blood-2010-08-301333}},
doi = {{10.1182/blood-2010-08-301333}},
volume = {{117}},
year = {{2011}},
}