HLA-A promoter, coding, and 3′UTR sequences in a Brazilian cohort, and their evolutionary aspects

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dc.contributor.authorLima, Thálitta H. A. [UNESP]
dc.contributor.authorSouza, Andreia S. [UNESP]
dc.contributor.authorPorto, Iane O. P. [UNESP]
dc.contributor.authorPaz, Michelle A. [UNESP]
dc.contributor.authorVeiga-Castelli, Luciana C.
dc.contributor.authorOliveira, Maria Luiza G.
dc.contributor.authorDonadi, Eduardo A.
dc.contributor.authorMeyer, Diogo
dc.contributor.authorSabbagh, Audrey
dc.contributor.authorMendes-Junior, Celso T.
dc.contributor.authorCastelli, Erick C. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionFaculté de Pharmacie
dc.date.accessioned2019-10-06T16:22:03Z
dc.date.available2019-10-06T16:22:03Z
dc.date.issued2019-02-01
dc.description.abstractHLA-A is the second most polymorphic locus of the human leucocyte antigen (HLA) complex encoding a key molecule for antigen presentation and NK cell modulation. Many studies have evaluated HLA-A variability in worldwide populations, focusing mainly on exons, but the regulatory segments have been poorly characterized. HLA-A variability is particularly high in the segment encoding the peptide-binding groove (exons 2 and 3), which is related to the antigen presentation function and the balancing selection in these segments. Here we evaluate the genetic diversity of the HLA-A gene considering a continuous segment encompassing the extended promoter (1.5 kb upstream of the first translated ATG), all exons and introns, and the entire 3′ untranslated region, by using massively parallel sequencing. To achieve this goal, we used a freely available bioinformatics workflow that optimizes read mapping for HLA genes and defines complete sequences using either the phase among variable sites directly observed in sequencing data and probabilistic models. The HLA-A variability detected in a highly admixed population sample from Brazil shows that the HLA-A regulatory segments present few, but divergent sequences. The regulatory segments are in close association with the coding alleles. Both exons and introns are highly variable. Moreover, patterns of molecular diversity suggest that the promoter, in addition to the coding region, might be under the same selective pressure, but a different scenario arises when it comes to exon 4 and the 3′UTR segment.en
dc.description.affiliationMolecular Genetics and Bioinformatics Laboratory - Experimental Research Unity School of Medicine São Paulo State University (UNESP)
dc.description.affiliationSão Paulo State University (UNESP) Genetics Program Institute of Biosciences of Botucatu
dc.description.affiliationPathology Program School of Medicine São Paulo State University (UNESP)
dc.description.affiliationDepartment of Genetics School of Medicine of Ribeirão Preto University of São Paulo (USP)
dc.description.affiliationDepartment of Medicine School of Medicine of Ribeirão Preto University of São Paulo (USP)
dc.description.affiliationDepartment of Genetics and Evolutionary Biology University of São Paulo
dc.description.affiliationUMR 216 MERIT IRD Université Paris Descartes Faculté de Pharmacie
dc.description.affiliationDepartamento de Química Faculdade de Filosofia Ciências e Letras de Ribeirão Preto Universidade de São Paulo
dc.description.affiliationUnespMolecular Genetics and Bioinformatics Laboratory - Experimental Research Unity School of Medicine São Paulo State University (UNESP)
dc.description.affiliationUnespSão Paulo State University (UNESP) Genetics Program Institute of Biosciences of Botucatu
dc.description.affiliationUnespPathology Program School of Medicine São Paulo State University (UNESP)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipIdFAPESP: 2013/17084-2
dc.description.sponsorshipIdFAPESP: 2016/03622-0
dc.format.extent65-79
dc.identifierhttp://dx.doi.org/10.1111/tan.13474
dc.identifier.citationHLA, v. 93, n. 2-3, p. 65-79, 2019.
dc.identifier.doi10.1111/tan.13474
dc.identifier.issn2059-2310
dc.identifier.issn2059-2302
dc.identifier.scopus2-s2.0-85063392155
dc.identifier.urihttp://hdl.handle.net/11449/188877
dc.language.isoeng
dc.relation.ispartofHLA
dc.rights.accessRightsAcesso restrito
dc.sourceScopus
dc.subjectalleles
dc.subjectbalancing selection
dc.subjectevolution
dc.subjecthaplotypes
dc.subjectHLA-A
dc.subjectnatural selection
dc.subjectnext generation sequencing—NGS
dc.subjectpolymorphisms
dc.titleHLA-A promoter, coding, and 3′UTR sequences in a Brazilian cohort, and their evolutionary aspectsen
dc.typeArtigo
unesp.author.orcid0000-0003-2142-7196[11]

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