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A novel B(weak) hybrid allele lacks three enhancer repeats but generates normal ABO transcript levels.

Thuresson, Britt LU ; Hosseini Maaf, Bahram LU ; Hult, Annika LU ; Hustinx, H; Alan Chester, M and Olsson, Martin L LU (2012) In Vox Sanguinis 102(1). p.55-64
Abstract
Background and Objectives Weak expression of A/B histo-blood group antigens is often explained by single nucleotide substitutions at the ABO locus. However, hybrid alleles containing segments from different ABO alleles can result in unexpected phenotypes and may complicate genotype analysis. We investigated the basis of weak B phenotype in a referred sample. Materials and Methods A healthy young woman was serologically phenotyped as AB(weak) and RBCs were characterized by flow cytometry. All seven ABO exons, five introns plus the 5'-region including the CCAAT-binding factor/Nuclear Factor Y (CBF/NF-Y) binding enhancer were sequenced. ABO transcript levels were measured in fresh peripheral blood samples. Expression of B antigen was... (More)
Background and Objectives Weak expression of A/B histo-blood group antigens is often explained by single nucleotide substitutions at the ABO locus. However, hybrid alleles containing segments from different ABO alleles can result in unexpected phenotypes and may complicate genotype analysis. We investigated the basis of weak B phenotype in a referred sample. Materials and Methods A healthy young woman was serologically phenotyped as AB(weak) and RBCs were characterized by flow cytometry. All seven ABO exons, five introns plus the 5'-region including the CCAAT-binding factor/Nuclear Factor Y (CBF/NF-Y) binding enhancer were sequenced. ABO transcript levels were measured in fresh peripheral blood samples. Expression of B antigen was semiquantified following transfection of HeLa cells. Results A new B(weak) allele with 53G>T resulted in a characteristic pattern of moderately weakened B antigen expression on RBCs. Its sequence revealed a novel hybrid between O(2) [O03] and B [B101] alleles with a crossingover region in intron 4 as defined by allele-specific polymorphisms. B transcript levels were similar to normal controls despite the O(2) -related single CBF/NF-Y-binding 43-bp motif in the enhancer region. Expression of the glycosyltransferase including the O(2) -specific Arg18Leu substitution resulted in a slight decrease in B-antigen-positive cells. Conclusion We describe here the first hybrid between an O(2) and a B allele and characterized the associated decrease in B antigen expression. Although it lacks three enhancer repeat units compared to common B alleles, the resulting transcript level was unaltered. This study challenges previous suggestions that the number of 43-bp motifs in the ABO enhancer determines transcription rates in erythroid cells. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
blood group, ABO, genetics, immunohaematology, RBC antigen and, antibodies, transcription
in
Vox Sanguinis
volume
102
issue
1
pages
55 - 64
publisher
Federation of European Neuroscience Societies and Blackwell Publishing Ltd
external identifiers
  • wos:000298602400008
  • pmid:21592135
  • scopus:84655162164
ISSN
1423-0410
DOI
10.1111/j.1423-0410.2011.01497.x
language
English
LU publication?
yes
id
0305427f-04b5-4b72-9084-88cc480efc40 (old id 1972372)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21592135?dopt=Abstract
date added to LUP
2011-06-07 21:15:40
date last changed
2017-01-01 06:18:20
@article{0305427f-04b5-4b72-9084-88cc480efc40,
  abstract     = {Background and Objectives Weak expression of A/B histo-blood group antigens is often explained by single nucleotide substitutions at the ABO locus. However, hybrid alleles containing segments from different ABO alleles can result in unexpected phenotypes and may complicate genotype analysis. We investigated the basis of weak B phenotype in a referred sample. Materials and Methods A healthy young woman was serologically phenotyped as AB(weak) and RBCs were characterized by flow cytometry. All seven ABO exons, five introns plus the 5'-region including the CCAAT-binding factor/Nuclear Factor Y (CBF/NF-Y) binding enhancer were sequenced. ABO transcript levels were measured in fresh peripheral blood samples. Expression of B antigen was semiquantified following transfection of HeLa cells. Results A new B(weak) allele with 53G>T resulted in a characteristic pattern of moderately weakened B antigen expression on RBCs. Its sequence revealed a novel hybrid between O(2) [O03] and B [B101] alleles with a crossingover region in intron 4 as defined by allele-specific polymorphisms. B transcript levels were similar to normal controls despite the O(2) -related single CBF/NF-Y-binding 43-bp motif in the enhancer region. Expression of the glycosyltransferase including the O(2) -specific Arg18Leu substitution resulted in a slight decrease in B-antigen-positive cells. Conclusion We describe here the first hybrid between an O(2) and a B allele and characterized the associated decrease in B antigen expression. Although it lacks three enhancer repeat units compared to common B alleles, the resulting transcript level was unaltered. This study challenges previous suggestions that the number of 43-bp motifs in the ABO enhancer determines transcription rates in erythroid cells.},
  author       = {Thuresson, Britt and Hosseini Maaf, Bahram and Hult, Annika and Hustinx, H and Alan Chester, M and Olsson, Martin L},
  issn         = {1423-0410},
  keyword      = {blood group,ABO,genetics,immunohaematology,RBC antigen and,antibodies,transcription},
  language     = {eng},
  number       = {1},
  pages        = {55--64},
  publisher    = {Federation of European Neuroscience Societies and Blackwell Publishing Ltd},
  series       = {Vox Sanguinis},
  title        = {A novel B(weak) hybrid allele lacks three enhancer repeats but generates normal ABO transcript levels.},
  url          = {http://dx.doi.org/10.1111/j.1423-0410.2011.01497.x},
  volume       = {102},
  year         = {2012},
}