title: HLA-E coding and 3' untranslated region variability determined by next-generation sequencing in two West-African population samples.
abstract: HLA-E is a non-classical Human Leucocyte Antigen class I gene with immunomodulatory properties. Whereas HLA-E expression usually occurs at low levels, it is widely distributed amongst human tissues, has the ability to bind self and non-self antigens and to interact with NK cells and T lymphocytes, being important for immunosurveillance and also for fighting against infections. HLA-E is usually the most conserved locus among all class I genes. However, most of the previous studies evaluating HLA-E variability sequenced only a few exons or genotyped known polymorphisms. Here we report a strategy to evaluate HLA-E variability by next-generation sequencing (NGS) that might be used to other HLA loci and present the HLA-E haplotype diversity considering the segment encoding the entire HLA-E mRNA (including 5'UTR, introns and the 3'UTR) in two African population samples, Susu from Guinea-Conakry and Lobi from Burkina Faso. Our results indicate that (a) the HLA-E gene is indeed conserved, encoding mainly two different protein molecules; (b) Africans do present several unknown HLA-E alleles presenting synonymous mutations; (c) the HLA-E 3'UTR is quite polymorphic and (d) haplotypes in the HLA-E 3'UTR are in close association with HLA-E coding alleles. NGS has proved to be an important tool on data generation for future studies evaluating variability in non-classical MHC genes.
authors.affiliation: School of Medicine of Botucatu, UNESP - Univ Estadual Paulista, Department of Pathology, Botucatu, State of São Paulo, Brazil. Electronic address: castelli@fmb.unesp.br.
authors.forename: Erick C
authors.initials: EC
authors.lastname: Castelli
authors.affiliation: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, 14040-901 Ribeirão Preto, SP, Brazil.
authors.forename: Celso T
authors.initials: CT
authors.lastname: Mendes-Junior
authors.affiliation: Institute of Research for Development, Mixed Research Unit 216 MERIT, Paris, France; Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Sabbagh
authors.affiliation: School of Medicine of Botucatu, UNESP - Univ Estadual Paulista, Department of Pathology, Botucatu, State of São Paulo, Brazil.
authors.forename: Iane O P
authors.initials: IO
authors.lastname: Porto
authors.affiliation: Institute of Research for Development, Mixed Research Unit 216 MERIT, Paris, France; Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: André
authors.initials: A
authors.lastname: Garcia
authors.affiliation: School of Medicine of Botucatu, UNESP - Univ Estadual Paulista, Department of Pathology, Botucatu, State of São Paulo, Brazil.
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Ramalho
authors.affiliation: School of Medicine of Botucatu, UNESP - Univ Estadual Paulista, Department of Pathology, Botucatu, State of São Paulo, Brazil.
authors.forename: Thálitta H A
authors.initials: TH
authors.lastname: Lima
authors.affiliation: Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo - USP, Ribeirão Preto, SP, Brazil.
authors.forename: Juliana D
authors.initials: JD
authors.lastname: Massaro
authors.affiliation: Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo - USP, Ribeirão Preto, SP, Brazil.
authors.forename: Fabrício C
authors.initials: FC
authors.lastname: Dias
authors.affiliation: Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo - USP, Ribeirão Preto, SP, Brazil.
authors.forename: Cristhianna V A
authors.initials: CV
authors.lastname: Collares
authors.affiliation: International Center for Development Research on Aging in Sub-Humid Areas (CIRDES), Bobo-Dioulasso, Burkina Faso; Institute of Research for Development, Mixed Research Unit IRD-CIRAD 177, Montpellier, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Jamonneau
authors.affiliation: Institute of Research for Development, Mixed Research Unit IRD-CIRAD 177, Montpellier, France; National Sleeping Sickness Control Program, Ministry of Health and Public Hygiene, Conakry, Guinea.
authors.forename: Bruno
authors.initials: B
authors.lastname: Bucheton
authors.affiliation: National Sleeping Sickness Control Program, Ministry of Health and Public Hygiene, Conakry, Guinea.
authors.forename: Mamadou
authors.initials: M
authors.lastname: Camara
authors.affiliation: Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirão Preto, University of São Paulo - USP, Ribeirão Preto, SP, Brazil.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
mesh_terms: D020413:3' Untranslated Regions; D000354:Africa, Western; D000483:Alleles; D044383:Black People / Q000235:genetics*; D005787:Gene Frequency; D014644:Genetic Variation; D005828:Genetics, Population; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D015810:Linkage Disequilibrium; D016366:Open Reading Frames; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D000097625:HLA-E Antigens
chemical_list: D020413:3' Untranslated Regions; D015395:Histocompatibility Antigens Class I; D000097625:HLA-E Antigens
keywords: Africa; HLA-E; Haplotypes; Next-generation sequencing (NGS); Non-classical HLA; Polymorphisms; West-African populations