PMID- 21741421
OWN - NLM
STAT- MEDLINE
DCOM- 20111227
LR  - 20110825
IS  - 1879-1166 (Electronic)
IS  - 0198-8859 (Linking)
VI  - 72
IP  - 9
DP  - 2011 Sep
TI  - A "silent" nucleotide substitution in exon 4 is responsible for the "alternative 
      expression" of HLA-A*01:01:38L through aberrant splicing.
PG  - 717-22
LID - 10.1016/j.humimm.2011.05.019 [doi]
AB  - A Welsh Bone Marrow Donor Registry donor was serologically typed, using both 
      alloantisera and monoclonal antibodies, as human leukocyte antigen (HLA)-A2, A-, 
      but typed by polymerase chain reaction sequence-specific priming as HLA-A*01, 
      A*02. Full gene sequencing of the A*01 separated allele indicated an apparently 
      normal A*01:01:01:01 apart from a silent change at nucleotide 705 in exon 4, 
      codon 211 (alanine: normally GCG but GCA in this donor). Sequence analysis of the 
      amplified A*01 allele in cDNA synthesized from RNA indicated that exons 1, 2, 3, 
      and 5 had typical A*01:01 sequences. However, exon 4 was truncated in this allele 
      (87 nucleotides shorter), beginning just after the single nucleotide polymorphism 
      (SNP) identified in genomic DNA sequencing. The nucleotide sequence up to, and 1 
      nucleotide after, the SNP is homologous with the 3' end of human leukocyte 
      antigen (HLA)-A intron 3 and thus resembles a splice site. However, a small 
      amount of "normal" HLA-A1 was detected on the surface of cells from an 
      Epstein-Barr virus transformed B-cell line (BCL), but not on peripheral blood 
      mononuclear cells, by flow cytometry. Additionally, a trace amount of "normal 
      sized" A*01 was amplified from cDNA. We suggest that in this A*01 variant allele 
      (A*01:01:38L) intron 3 is largely spliced out with a part of exon 4; exon 4 is 
      still in-frame but the protein is smaller than the wild type. This is likely to 
      affect folding and assembly of the "wild type" mature protein on the cell 
      surface, thus explaining the apparent null phenotype when assayed by conventional 
      serology. However, a small amount of A1 protein is made from correctly spliced 
      A*01 mRNA and is detectable on BCLs using flow cytometry.
CI  - Copyright (c) 2011 American Society for Histocompatibility and Immunogenetics. 
      Published by Elsevier Inc. All rights reserved.
FAU - Dunn, Paul P J
AU  - Dunn PP
AD  - Tissue Typing Laboratory, New Zealand Blood Service, Auckland, New Zealand. 
      paul.dunn@nzblood.co.nz
FAU - Hammond, Laura
AU  - Hammond L
FAU - Coates, Ernest
AU  - Coates E
FAU - Street, Jane
AU  - Street J
FAU - Griner, Leon
AU  - Griner L
FAU - Darke, Christopher
AU  - Darke C
LA  - eng
PT  - Journal Article
DEP - 20110624
PL  - United States
TA  - Hum Immunol
JT  - Human immunology
JID - 8010936
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (HLA-A*01:01 antigen)
RN  - 0 (HLA-A1 Antigen)
RN  - 0 (Nucleotides)
SB  - IM
MH  - Alternative Splicing/immunology
MH  - Antibodies, Monoclonal/metabolism
MH  - B-Lymphocytes/cytology/*metabolism
MH  - Blood Grouping and Crossmatching
MH  - Bone Marrow Transplantation
MH  - Cell Line, Transformed
MH  - Cell Separation
MH  - Exons/genetics
MH  - Flow Cytometry
MH  - Gene Expression Regulation/immunology
MH  - HLA-A1 Antigen/genetics/*metabolism
MH  - Histocompatibility Testing
MH  - Humans
MH  - Leukocytes, Mononuclear/cytology/*metabolism
MH  - Nucleotides/genetics
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single Nucleotide
MH  - Sequence Deletion/genetics
EDAT- 2011/07/12 06:00
MHDA- 2011/12/28 06:00
CRDT- 2011/07/12 06:00
PHST- 2009/07/28 00:00 [received]
PHST- 2011/04/15 00:00 [revised]
PHST- 2011/05/13 00:00 [accepted]
PHST- 2011/07/12 06:00 [entrez]
PHST- 2011/07/12 06:00 [pubmed]
PHST- 2011/12/28 06:00 [medline]
AID - S0198-8859(11)00126-1 [pii]
AID - 10.1016/j.humimm.2011.05.019 [doi]
PST - ppublish
SO  - Hum Immunol. 2011 Sep;72(9):717-22. doi: 10.1016/j.humimm.2011.05.019. Epub 2011 
      Jun 24.