PMID- 27976839
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 2059-2310 (Electronic)
IS  - 2059-2302 (Print)
IS  - 2059-2302 (Linking)
VI  - 89
IP  - 1
DP  - 2017 Jan
TI  - Limited HLA sequence variation outside of antigen recognition domain exons of 360 
      10 of 10 matched unrelated hematopoietic stem cell transplant donor-recipient 
      pairs.
PG  - 39-46
LID - 10.1111/tan.12942 [doi]
AB  - Traditional DNA-based typing focuses primarily on interrogating the exons of 
      human leukocyte antigen (HLA) genes that form the antigen recognition domain 
      (ARD). The relevance of mismatching donor and recipient for HLA variation outside 
      the ARD on hematopoietic stem cell transplantation (HSCT) outcomes is unknown. 
      This study was designed to evaluate the frequency of variation outside the ARD in 
      10 of 10 (HLA-A, -B, -C, -DRB1, -DQB1) matched unrelated donor transplant pairs 
      (n = 360). Next-generation DNA sequencing was used to characterize both HLA exons 
      and introns for HLA-A, -B, -C alleles; exons 2, 3 and the intervening intron for 
      HLA-DRB1 and exons only for HLA-DQA1 and -DQB1. Over 97% of alleles at each locus 
      were matched for their nucleotide sequence outside of the ARD exons. Of the 4320 
      allele comparisons overall, only 17 allele pairs were mismatched for non-ARD 
      exons, 41 for noncoding regions and 9 for ARD exons. The observed variation 
      between donor and recipient usually involved a single nucleotide difference (88% 
      of mismatches); 88% of the non-ARD exon variants impacted the amino acid 
      sequence. The impact of amino acid sequence variation caused by substitutions in 
      exons outside ARD regions in D-R pairs will be difficult to assess in HSCT 
      outcome studies because these mismatches do not occur very frequently.
CI  - (c) 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
FAU - Hou, L
AU  - Hou L
AD  - Department of Pediatrics, Georgetown University, Washington, DC, USA.
FAU - Vierra-Green, C
AU  - Vierra-Green C
AD  - Center for International Blood and Marrow Transplant Research, Minneapolis, MN, 
      USA.
FAU - Lazaro, A
AU  - Lazaro A
AD  - Department of Pediatrics, Georgetown University, Washington, DC, USA.
FAU - Brady, C
AU  - Brady C
AD  - Center for International Blood and Marrow Transplant Research, Minneapolis, MN, 
      USA.
FAU - Haagenson, M
AU  - Haagenson M
AD  - Center for International Blood and Marrow Transplant Research, Minneapolis, MN, 
      USA.
FAU - Spellman, S
AU  - Spellman S
AD  - Center for International Blood and Marrow Transplant Research, Minneapolis, MN, 
      USA.
FAU - Hurley, C K
AU  - Hurley CK
AD  - Department of Pediatrics, Georgetown University, Washington, DC, USA.
AD  - Department of Oncology, Georgetown University, Washington, DC, USA.
LA  - eng
GR  - U10 HL069294/HL/NHLBI NIH HHS/United States
GR  - U24 CA076518/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20161215
PL  - England
TA  - HLA
JT  - HLA
JID - 101675570
PMC - PMC5425813
MID - NIHMS857760
OTO - NOTNLM
OT  - deoxyribonucleic acid
OT  - genetic
OT  - hematopoietic stem cell transplantation
OT  - histocompatibility testing
OT  - human leukocyte antigens
OT  - polymorphism
OT  - sequence analysis
COIS- Conflicts of interest: Georgetown University has filed a patent application on 
      which coauthor Hurley is an inventor of the HLA typing and Sanger-based 
      sequencing technology.
EDAT- 2016/12/16 06:00
MHDA- 2016/12/16 06:01
PMCR- 2018/01/01
CRDT- 2016/12/16 06:00
PHST- 2016/08/26 00:00 [received]
PHST- 2016/10/24 00:00 [revised]
PHST- 2016/11/17 00:00 [accepted]
PHST- 2016/12/16 06:00 [pubmed]
PHST- 2016/12/16 06:01 [medline]
PHST- 2016/12/16 06:00 [entrez]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.1111/tan.12942 [doi]
PST - ppublish
SO  - HLA. 2017 Jan;89(1):39-46. doi: 10.1111/tan.12942. Epub 2016 Dec 15.