PMID- 27679434
OWN - NLM
STAT- MEDLINE
DCOM- 20170601
LR  - 20190722
IS  - 1530-8561 (Electronic)
IS  - 0009-9147 (Linking)
VI  - 62
IP  - 12
DP  - 2016 Dec
TI  - Generation of Full-Length Class I Human Leukocyte Antigen Gene Consensus 
      Sequences for Novel Allele Characterization.
PG  - 1630-1638
AB  - BACKGROUND: Routine, high-resolution human leukocyte antigen (HLA) genotyping by 
      next generation sequencing within clinical immunogenetics laboratories can now 
      provide the full-length gene sequence characterization of fully phased HLA 
      alleles. This powerful technique provides insights into HLA variation beyond the 
      traditionally characterized antigen recognition domain, providing sequence 
      annotation across the entire gene including untranslated and intronic regions and 
      may be used to characterize novel alleles from massively parallel sequencing 
      runs. METHODS: We evaluated the utility of the Omixon Holotype HLA assay to 
      generate credible, fully phased full-length gene consensus sequences for 50 
      individuals at major histocompatibility complex, class I, A (HLA-A), HLA-B, and 
      HLA-C loci (300 genotyped alleles in total) to identify and characterize novel 
      class I HLA alleles using our downstream analytical pipeline. RESULTS: Our 
      analysis revealed that 7.7% (23/300) of genotyped class I HLA alleles contain 
      novel polymorphisms. Interestingly, all of the novel alleles identified by our 
      analysis were found to harbor sequence variations within intronic regions of the 
      respective locus. In total our analysis identified 17 unique novel class I HLA 
      alleles from 23 of the 300 genotyped alleles and generated full-length gene 
      sequence annotations for 9 previously incompletely annotated HLA class I allele 
      sequences derived from 14 of the 300 genotyped alleles. CONCLUSIONS: The 
      demonstrated utility of the Omixon Holotype HLA assay in combination with our 
      downstream analytical framework to generate fully phased, full-length gene 
      consensus sequences for the identification and characterization of novel HLA 
      alleles, facilitates the study of HLA polymorphism beyond the antigen recognition 
      domain in human health and disease.
CI  - (c) 2016 American Association for Clinical Chemistry.
FAU - Clark, Peter M
AU  - Clark PM
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, PA.
FAU - Duke, Jamie L
AU  - Duke JL
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, PA.
FAU - Ferriola, Deborah
AU  - Ferriola D
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, PA.
FAU - Bravo-Egana, Valia
AU  - Bravo-Egana V
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, PA.
FAU - Vago, Tunde
AU  - Vago T
AD  - Omixon Biocomputing, Budapest, Hungary.
FAU - Hassan, Aniqa
AU  - Hassan A
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, PA.
FAU - Papazoglou, Anna
AU  - Papazoglou A
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, PA.
FAU - Monos, Dimitri
AU  - Monos D
AD  - Department of Pathology and Laboratory Medicine, The Children's Hospital of 
      Philadelphia, Philadelphia, PA; monosd@email.chop.edu.
AD  - Department of Pathology and Lab Medicine, Perelman School of Medicine, University 
      of Pennsylvania, Philadelphia, PA.
LA  - eng
PT  - Journal Article
DEP - 20160927
PL  - England
TA  - Clin Chem
JT  - Clinical chemistry
JID - 9421549
RN  - 0 (Histocompatibility Antigens Class I)
SB  - IM
MH  - Algorithms
MH  - *Alleles
MH  - *Consensus Sequence
MH  - Genotype
MH  - *High-Throughput Nucleotide Sequencing
MH  - Histocompatibility Antigens Class I/*genetics
MH  - Humans
EDAT- 2016/09/30 06:00
MHDA- 2017/06/02 06:00
CRDT- 2016/09/29 06:00
PHST- 2016/05/20 00:00 [received]
PHST- 2016/08/19 00:00 [accepted]
PHST- 2016/09/30 06:00 [pubmed]
PHST- 2017/06/02 06:00 [medline]
PHST- 2016/09/29 06:00 [entrez]
AID - clinchem.2016.260661 [pii]
AID - 10.1373/clinchem.2016.260661 [doi]
PST - ppublish
SO  - Clin Chem. 2016 Dec;62(12):1630-1638. doi: 10.1373/clinchem.2016.260661. Epub 
      2016 Sep 27.