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Weak A phenotypes associated with novel ABO alleles carrying the A(2)-related 1061C deletion and various missense substitutions.

Hult, Annika LU ; Yazer, Mark H; Jørgensen, René; Hellberg, Åsa LU ; Hustinx, Hein; Peyrard, Thierry; Palcic, Monica M and Olsson, Martin L LU (2010) In Transfusion 50. p.1471-1486
Abstract
BACKGROUND: The 1061delC single-nucleotide polymorphism (SNP) has been reported mostly in the context of the common A(2)[A201] allele and typically produces an A(2) phenotype. This study evaluated new A(weak) alleles, each containing 1061delC. STUDY DESIGN AND METHODS: Twenty samples were referred to our laboratory for analysis due to suspected A(weak) phenotypes originally detected at the referring centers. ABO Exons 1 through 7 and flanking intronic regions were sequenced. A antigen expression on red blood cells was analyzed by flow cytometry. Plasma enzyme activity was studied in one case. Molecular three-dimensional modeling techniques studied the potential effects of amino acid changes on the resulting glycosyltransferases (GTs).... (More)
BACKGROUND: The 1061delC single-nucleotide polymorphism (SNP) has been reported mostly in the context of the common A(2)[A201] allele and typically produces an A(2) phenotype. This study evaluated new A(weak) alleles, each containing 1061delC. STUDY DESIGN AND METHODS: Twenty samples were referred to our laboratory for analysis due to suspected A(weak) phenotypes originally detected at the referring centers. ABO Exons 1 through 7 and flanking intronic regions were sequenced. A antigen expression on red blood cells was analyzed by flow cytometry. Plasma enzyme activity was studied in one case. Molecular three-dimensional modeling techniques studied the potential effects of amino acid changes on the resulting glycosyltransferases (GTs). RESULTS: Thirteen alleles were discovered, each featuring 1061delC with at least 1 of 12 additional SNPs in the coding region. One of these SNPs disrupts the translation initiation codon. Another constitutes the first reported change in the DVD motif. One SNP found in three alleles causes a substitution of one of the four amino acids that differentiates the wild-type A and B enzymes but plasma enzyme analysis by two methods showed only slightly decreased or normal A(2) activity. Flow cytometric analysis semiquantified the A antigen levels in 16 cases featuring 10 of the alleles and ranged from very weak to nearly A(2) levels. However, the majority of the samples displayed A(x)-like patterns. Molecular modeling of some of the GT variants indicated conformational changes that may explain the diminished A expression observed. CONCLUSION: Missense SNPs were identified in 13 novel A(2)-like alleles, which produced a variety of A subgroup phenotypes. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Transfusion
volume
50
pages
1471 - 1486
publisher
Wiley-Blackwell
external identifiers
  • WOS:000279453400011
  • PMID:20456702
  • Scopus:77954340282
ISSN
1537-2995
DOI
10.1111/j.1537-2995.2010.02670.x
language
English
LU publication?
yes
id
c93a27e7-909a-4c76-b33d-93c486f3608e (old id 1610395)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20456702?dopt=Abstract
date added to LUP
2010-06-01 20:58:31
date last changed
2016-12-04 04:41:23
@misc{c93a27e7-909a-4c76-b33d-93c486f3608e,
  abstract     = {BACKGROUND: The 1061delC single-nucleotide polymorphism (SNP) has been reported mostly in the context of the common A(2)[A201] allele and typically produces an A(2) phenotype. This study evaluated new A(weak) alleles, each containing 1061delC. STUDY DESIGN AND METHODS: Twenty samples were referred to our laboratory for analysis due to suspected A(weak) phenotypes originally detected at the referring centers. ABO Exons 1 through 7 and flanking intronic regions were sequenced. A antigen expression on red blood cells was analyzed by flow cytometry. Plasma enzyme activity was studied in one case. Molecular three-dimensional modeling techniques studied the potential effects of amino acid changes on the resulting glycosyltransferases (GTs). RESULTS: Thirteen alleles were discovered, each featuring 1061delC with at least 1 of 12 additional SNPs in the coding region. One of these SNPs disrupts the translation initiation codon. Another constitutes the first reported change in the DVD motif. One SNP found in three alleles causes a substitution of one of the four amino acids that differentiates the wild-type A and B enzymes but plasma enzyme analysis by two methods showed only slightly decreased or normal A(2) activity. Flow cytometric analysis semiquantified the A antigen levels in 16 cases featuring 10 of the alleles and ranged from very weak to nearly A(2) levels. However, the majority of the samples displayed A(x)-like patterns. Molecular modeling of some of the GT variants indicated conformational changes that may explain the diminished A expression observed. CONCLUSION: Missense SNPs were identified in 13 novel A(2)-like alleles, which produced a variety of A subgroup phenotypes.},
  author       = {Hult, Annika and Yazer, Mark H and Jørgensen, René and Hellberg, Åsa and Hustinx, Hein and Peyrard, Thierry and Palcic, Monica M and Olsson, Martin L},
  issn         = {1537-2995},
  language     = {eng},
  pages        = {1471--1486},
  publisher    = {ARRAY(0x849e768)},
  series       = {Transfusion},
  title        = {Weak A phenotypes associated with novel ABO alleles carrying the A(2)-related 1061C deletion and various missense substitutions.},
  url          = {http://dx.doi.org/10.1111/j.1537-2995.2010.02670.x},
  volume       = {50},
  year         = {2010},
}