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Extended HLA-G genetic diversity and ancestry composition in a Brazilian admixed population sample: Implications for HLA-G transcriptional control and for case-control association studies

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Guimaraes de Oliveira, Maria Luiza [1] ; Veiga-Castellia, Luciana Caricati [1] ; Marcorin, Leticia [1] ; Debortoli, Guilherme [1] ; Eburneo Pereira, Alison Luis [1] ; de Aguiar Fracasso, Nadia Carolina [1] ; Silva, Guilherme do Valle [2] ; Souza, Andreia S. [3] ; Massaro, Juliana Doblas [4] ; Simoes, Aguinaldo Luiz [1] ; Sabbagh, Audrey [5] ; Donadi, Eduardo Antonio [4] ; Castelli, Erick C. [3] ; Mendes-Junior, Celso Teixeira [2]
Número total de Autores: 14
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Genet, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Dept Quim, Lab Pesquisas Forenses & Genom, Fac Filosofia Ciencias & Letras Ribeirao Preto, Ave Bandeirantes 3900, BR-14040901 Ribeirao Preto, SP - Brazil
[3] Sao Paulo State Univ UNESP, Mol Genet & Bioinformat Lab, Sch Med, Botucatu, SP - Brazil
[4] Univ Sao Paulo, Dept Clin Med, Fac Med Ribeirao Preto, BR-14049900 Ribeirao Preto, SP - Brazil
[5] Univ Paris 05, Fac Pharm Paris, UMR 216, IRD MERIT, Paris - France
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: HUMAN IMMUNOLOGY; v. 79, n. 11, p. 790-799, NOV 2018.
Citações Web of Science: 0
Resumo

Human leukocyte antigen-G (HLA-G) is a nonclassical Major Histocompatibility Complex (MHC) molecule with immunomodulatory function and restricted tissue expression. The genetic diversity of HLA-G has been extensively studied in several populations, however, the segment located upstream -1406 has not yet been evaluated. We characterized the nucleotide variation and haplotype structure of an extended distal region (-2635), all exons and the 3'UTR segment of HLA-G by next-generation sequencing (NGS) in a sample of 335 Brazilian individuals. We detected 29 variants at the HLA-G distal promoter region, arranged into 19 haplotypes, among which we identified sites that may influence transcription factor targeting. Although the variation pattern in the distal region resembled the one observed in the conventional promoter segment, molecular signature for balancing selection was observed in the promoter segment from -1406 to -1 (Tajima's D = 2.315, P = 0.017), but not in this distal segment (D = 1.049, P = 0.118). Furthermore, the ancestry composition of this Brazilian population sample was determined by the analysis of SNPforID 34-plex ancestry informative marker (AIM) SNP panel. The distribution of HLA-G haplotypes was ancestry-dependent, corroborating previous findings and emphasizing the importance of considering the ancestry information in association studies. (AU)

Processo FAPESP: 13/15447-0 - Sequenciamento de nova geração das regiões regulatórias e exônicas de dez genes envolvidos na biossíntese de melanina em amostra da população brasileira
Beneficiário:Celso Teixeira Mendes Junior
Linha de fomento: Auxílio à Pesquisa - Regular