title: HLA-G variability and haplotypes detected by massively parallel sequencing procedures in the geographicaly distinct population samples of Brazil and Cyprus.
abstract: The HLA-G molecule presents immunomodulatory properties that might inhibit immune responses when interacting with specific Natural Killer and T cell receptors, such as KIR2DL4, ILT2 and ILT4. Thus, HLA-G might influence the outcome of situations in which fine immune system modulation is required, such as autoimmune diseases, transplants, cancer and pregnancy. The majority of the studies regarding the HLA-G gene variability so far was restricted to a specific gene segment (i.e., promoter, coding or 3' untranslated region), and was performed by using Sanger sequencing and probabilistic models to infer haplotypes. Here we propose a massively parallel sequencing (NGS) with a bioinformatics strategy to evaluate the entire HLA-G regulatory and coding segments, with haplotypes inferred relying more on the straightforward haplotyping capabilities of NGS, and less on probabilistic models. Then, HLA-G variability was surveyed in two admixed population samples of distinct geographical regions and demographic backgrounds, Cyprus and Brazil. Most haplotypes (promoters, coding, 3'UTR and extended ones) were detected both in Brazil and Cyprus and were identical to the ones already described by probabilistic models, indicating that these haplotypes are quite old and may be present worldwide.
authors.affiliation: Department of Pathology, School of Medicine, UNESP - Univ. Estadual Paulista, Botucatu, State of São Paulo, Brazil; Molecular Genetics and Bioinformatics Laboratory, Experimental Research Unit (UNIPEX), Sector 5, School of Medicine, UNESP - Univ. Estadual Paulista, Botucatu, State of São Paulo, Brazil. Electronic address: castelli@fmb.unesp.br.
authors.forename: Erick C
authors.initials: EC
authors.lastname: Castelli
authors.affiliation: Karaiskakio Foundation, Nicosia, Cyprus.
authors.forename: Petroula
authors.initials: P
authors.lastname: Gerasimou
authors.affiliation: Molecular Genetics and Bioinformatics Laboratory, Experimental Research Unit (UNIPEX), Sector 5, School of Medicine, UNESP - Univ. Estadual Paulista, Botucatu, State of São Paulo, Brazil.
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Paz
authors.affiliation: Molecular Genetics and Bioinformatics Laboratory, Experimental Research Unit (UNIPEX), Sector 5, School of Medicine, UNESP - Univ. Estadual Paulista, Botucatu, State of São Paulo, Brazil.
authors.forename: Jaqueline
authors.initials: J
authors.lastname: Ramalho
authors.affiliation: Molecular Genetics and Bioinformatics Laboratory, Experimental Research Unit (UNIPEX), Sector 5, School of Medicine, UNESP - Univ. Estadual Paulista, Botucatu, State of São Paulo, Brazil.
authors.forename: Iane O P
authors.initials: IOP
authors.lastname: Porto
authors.affiliation: Molecular Genetics and Bioinformatics Laboratory, Experimental Research Unit (UNIPEX), Sector 5, School of Medicine, UNESP - Univ. Estadual Paulista, Botucatu, State of São Paulo, Brazil.
authors.forename: Thálitta H A
authors.initials: THA
authors.lastname: Lima
authors.affiliation: Molecular Genetics and Bioinformatics Laboratory, Experimental Research Unit (UNIPEX), Sector 5, School of Medicine, UNESP - Univ. Estadual Paulista, Botucatu, State of São Paulo, Brazil.
authors.forename: Andréia S
authors.initials: AS
authors.lastname: Souza
authors.affiliation: Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirão Preto, University of the State of São Paulo (USP), Ribeirão Preto, State of São Paulo, Brazil.
authors.forename: Luciana C
authors.initials: LC
authors.lastname: Veiga-Castelli
authors.affiliation: Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirão Preto, University of the State of São Paulo (USP), Ribeirão Preto, State of São Paulo, Brazil.
authors.forename: Cristhianna V A
authors.initials: CVA
authors.lastname: Collares
authors.affiliation: Division of Clinical Immunology, Department of Medicine, School of Medicine of Ribeirão Preto, University of the State of São Paulo (USP), Ribeirão Preto, State of São Paulo, Brazil.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
authors.affiliation: Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Celso T
authors.initials: CT
authors.lastname: Mendes-Junior
authors.affiliation: Karaiskakio Foundation, Nicosia, Cyprus.
authors.forename: Paul
authors.initials: P
authors.lastname: Costeas
mesh_terms: D000328:Adult; D001483:Base Sequence; D001938:Brazil; D019295:Computational Biology; D003535:Cyprus; D005260:Female; D014644:Genetic Variation; D059951:HLA-G Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction
chemical_list: D059951:HLA-G Antigens
keywords: Brazil; Cyprus; HLA-G; Haplotypes; Massive parallel sequencing; NGS; Next generation sequencing; Polymorphisms; Variability