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Worldwide genetic variation at the 3′ untranslated region of the HLA-G gene: balancing selection influencing genetic diversity

Genes & Immunity volume 15, pages 95–106 (2014)Cite this article

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Abstract

The HLA-G (human leukocyte antigen-G) molecule plays a pivotal role in immune tolerance by inhibiting different cell subsets involved in both innate and adaptive immunity. Besides its primary function in maintaining the maternal–fetal tolerance, HLA-G has been involved in a wide range of pathological conditions where it can be either favorable or detrimental to the patient, depending on the nature of the pathology. Although several studies have demonstrated the utmost importance of the 3′ untranslated region (3′UTR) in the HLA-G expression profile, limited data exist on the sequence variability of this gene region in human populations. In this study, we characterized the genetic diversity and haplotype structure of the HLA-G 3′UTR by resequencing 444 individuals from three sub-Saharan African populations and retrieving data from the 1000 Genomes project and the literature. A total of 1936 individuals representing 21 worldwide populations were combined and jointly analyzed. Our data revealed a high level of nucleotide diversity, an excess of intermediate frequency variants and an extremely low population differentiation, strongly supporting a history of balancing selection at this locus. The 14-bp insertion/deletion polymorphism was further pointed out as the likely target of selection, emphasizing its potential role in the post-transcriptional regulation of HLA-G expression.

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Acknowledgements

This work was supported by the binational collaborative research program CAPES-COFECUB (Grant 653/09) and by the Spanish National Institute for Bioinformatics (www.inab.org). PL is supported by a PhD fellowship from ‘Acción Estratrégica de Salud, en el Marco del Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica 2008–2011’ from Instituto de Salud Carlos III. We deeply thank Txema Heredia, Angel Carreno and Jordi Rambla for computational support.

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  1. A Sabbagh and P Luisi: These authors contributed equally to this work.

Authors and Affiliations

  1. Institut de Recherche pour le Développement, UMR 216 Mère et enfant face aux infections tropicales, Paris, France

    A Sabbagh, L Gineau & A Garcia

  2. Faculté de Pharmacie, Université Paris Descartes, Sorbonne Paris Cité, Paris, France

    A Sabbagh, L Gineau & A Garcia

  3. Institute of Evolutionary Biology, CEXS-UPF-PRBB, Catalonia, Barcelona, Spain

    P Luisi & H Laayouni

  4. Department of Pathology, School of Medicine of Botucatu, University of the State of São Paulo–UNESP, Botucatu-SP, Brazil

    E C Castelli

  5. IRD, UMR 216, Centre d’Etude et de Recherche sur le Paludisme Associé à la Grossesse et à l’Enfance (CERPAGE); Faculté des Sciences de la Santé,

    D Courtin & J Milet

  6. Faculté des Sciences de la Santé, Cotonou, Bénin

    D Courtin & J Milet

  7. Division of Clinical Immunology, School of Medicine of Ribeirão Preto, University of São Paulo, São Paulo, Brazil

    J D Massaro & E A Donadi

  8. CEA, Service de Recherches en Hémato-Immunologie, iMETI, Hôpital Saint-Louis, Paris, France

    P Moreau

  9. Université Paris Diderot, Sorbonne Paris Cité, UMR E5, Institut Universitaire d’Hématologie, Hôpital Saint-Louis, Paris, France

    P Moreau

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  1. A Sabbagh
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Sabbagh, A., Luisi, P., Castelli, E. et al. Worldwide genetic variation at the 3′ untranslated region of the HLA-G gene: balancing selection influencing genetic diversity. Genes Immun 15, 95–106 (2014). https://doi.org/10.1038/gene.2013.67

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