title: New insights in HLA-E polymorphism by refined analysis of the full-length gene.
abstract: Human leukocyte antigen (HLA)-E is a non-classical HLA class I molecule that plays a role in both the innate and the adaptive immune response through interaction with receptors on natural killer- and T-cells. The HLA-E gene is characterized by limited polymorphism compared with the classical HLA loci on chromosome 6. At the start of this study, only 13 variable sites had been identified (IPD-IMGT/HLA Database v3.18.0). While most previous studies focused on polymorphism in exons 2 and 3 or specific gene regions, polymorphism in the other exons and introns could influence protein expression and function as well. Studies that investigate extended HLA-E polymorphism are therefore needed to better understand the functional relevance of HLA-E in health and disease.
  
  
  
  The aim of this study was to examine the variability of the full-length HLA-E gene region in individuals originating from different populations.
  
  
  
  A total of 7 new HLA-E alleles were identified using full-length HLA-E sequencing of 123 individuals from Asian, Dutch or Hunan Han origin. Furthermore, genome variation analysis of the third phase of the 1000 genomes database showed 107 new variable sites in 2504 individuals originating from 26 different populations.
  
  
  
  Our study demonstrates that the nucleotide variability of the HLA-E gene is much higher than previously known, albeit in only a limited number of individuals. Overall only 2 variants, HLA-E*01:01 and *01:03, are frequently present worldwide, suggesting that balancing selection is acting on HLA-E.
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: T I
authors.initials: TI
authors.lastname: Olieslagers
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: C E M
authors.initials: CE
authors.lastname: Voorter
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Groeneweg
authors.affiliation: Immunogenetics Laboratory, Shenzhen Blood Center, Shenzhen, China.
authors.forename: Y
authors.identifier: 0000-0002-4546-2191
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: L
authors.initials: L
authors.lastname: Wieten
authors.affiliation: Transplantation Immunology, Tissue Typing Laboratory, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: M G J
authors.initials: MG
authors.lastname: Tilanus
mesh_terms: D056704:Adaptive Immunity; D000483:Alleles; D044466:Asian People; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D005091:Exons; D015870:Gene Expression; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006650:Histocompatibility Testing; D016045:Human Genome Project; D006801:Humans; D007113:Immunity, Innate; D007438:Introns; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology; D011110:Polymorphism, Genetic; D020033:Protein Isoforms / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D044465:White People; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D020033:Protein Isoforms; D000097625:HLA-E Antigens
keywords: 
  HLA-E; 1000 genomes analysis; full-length gene polymorphism; human leukocyte antigens; sequence-based typing; single nucleotide polymorphism