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Non-classical HLA-E gene variability in Brazilians: a nearly invariable locus surrounded by the most variable genes in the human genome

Authors

  • L. C. Veiga-Castelli,

    Corresponding author
    1. Divisão de Imunologia Clínica, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brasil
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  • E. C. Castelli,

    1. Instituto de Ciências Biológicas, Universidade Federal de Goiás (UFG), Goiânia, GO, Brasil
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  • C. T. Mendes Jr,

    1. Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil
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  • W. A. da Silva Jr,

    1. Departamento de Genética, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo (USP), Ribeirão Preto, SP, Brasil
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  • M.-C. Faucher,

    1. Laboratoire d’immunogénétique, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, Canada
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  • K. Beauchemin,

    1. Laboratoire d’immunogénétique, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, Canada
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  • M. Roger,

    1. Laboratoire d’immunogénétique, Centre de Recherche du Centre Hospitalier de l’Université de Montréal (CRCHUM), Montréal, Canada
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  • P. Moreau,

    1. Commissariat à l’Energie Atomique et aux Energies Alternatives, Université Paris 7/DSV/I2BM/Service de Recherches en Hémato-Immunologie, IUH, Hôpital Saint-Louis, Paris, France
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  • E. A. Donadi

    1. Divisão de Imunologia Clínica, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto (FMRP), Universidade de São Paulo (USP), Ribeirão Preto, SP, Brasil
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Luciana C. Veiga-Castelli
Divisão de Imunologia Clínica
Departamento de Clínica Médica
Faculdade de Medicina de Ribeirão Preto (FMRP)
Universidade de São Paulo (USP)
Ribeirão Preto,
São Paulo 14049-900
Brasil
Tel: +55 16 3602 2566
Fax: +55 16 3633 6695
e-mail: luciana.veigacastelli@gmail.com

Abstract

The non-classical human leukocyte antigen (HLA) class I genes present a very low rate of variation. So far, only 10 HLA-E alleles encoding three proteins have been described, but only two are frequently found in worldwide populations. Because of its historical background, Brazilians are very suitable for population genetic studies. Therefore, 104 bone marrow donors from Brazil were evaluated for HLA-E exons 1–4. Seven variation sites were found, including two known single nucleotide polymorphisms (SNPs) at positions +424 and +756 and five new SNPs at positions +170 (intron 1), +1294 (intron 3), +1625, +1645 and +1857 (exon 4). Haplotyping analysis did show eight haplotypes, three of them known as E*01:01:01, E*01:03:01 and E*01:03:02:01 and five HLA-E new alleles that carry the new variation sites. The HLA-E*01:01:01 allele was the predominant haplotype (62.50%), followed by E*01:03:02:01 (24.52%). Selective neutrality tests have disclosed an interesting pattern of selective pressures in which balancing selection is probably shaping allele frequency distributions at an SNP at exon 3 (codon 107), sequence diversity at exon 4 and the non-coding regions is facing significant purifying pressure. Even in an admixed population such as the Brazilian one, the HLA-E locus is very conserved, presenting few polymorphic SNPs in the coding region.

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