title: HLA-F coding and regulatory segments variability determined by massively parallel sequencing procedures in a Brazilian population sample.
abstract: Human Leucocyte Antigen F (HLA-F) is a non-classical HLA class I gene distinguished from its classical counterparts by low allelic polymorphism and distinctive expression patterns. Its exact function remains unknown. It is believed that HLA-F has tolerogenic and immune modulatory properties. Currently, there is little information regarding the HLA-F allelic variation among human populations and the available studies have evaluated only a fraction of the HLA-F gene segment and/or have searched for known alleles only. Here we present a strategy to evaluate the complete HLA-F variability including its 5' upstream, coding and 3' downstream segments by using massively parallel sequencing procedures. HLA-F variability was surveyed on 196 individuals from the Brazilian Southeast. The results indicate that the HLA-F gene is indeed conserved at the protein level, where thirty coding haplotypes or coding alleles were detected, encoding only four different HLA-F full-length protein molecules. Moreover, a same protein molecule is encoded by 82.45% of all coding alleles detected in this Brazilian population sample. However, the HLA-F nucleotide and haplotype variability is much higher than our current knowledge both in Brazilians and considering the 1000 Genomes Project data. This protein conservation is probably a consequence of the key role of HLA-F in the immune system physiology.
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 Hetamaro Ayala
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: Renato Vidal
authors.initials: RV
authors.lastname: Buttura
authors.affiliation: School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, State of São Paulo, Brazil.
authors.forename: Eduardo Antônio
authors.initials: EA
authors.lastname: Donadi
authors.affiliation: School of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, State of São Paulo, Brazil.
authors.forename: Luciana Caricati
authors.initials: LC
authors.lastname: Veiga-Castelli
authors.affiliation: Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil.
authors.forename: Celso Teixeira
authors.initials: CT
authors.lastname: Mendes-Junior
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; Pathology Department, 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
mesh_terms: D001938:Brazil; D005006:Ethnicity; D005787:Gene Frequency; D005828:Genetics, Population; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006650:Histocompatibility Testing; D006801:Humans; D007107:Immune System / Q000502:physiology*; D056747:Immunomodulation; D016366:Open Reading Frames / Q000235:genetics*; D011110:Polymorphism, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*
chemical_list: C062341:HLA-F antigens; D015395:Histocompatibility Antigens Class I
keywords: HLA-F; Haplotypes; MHC; NGS; Next Generation Sequencing; Polymorphisms; Variability