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Title

Balancing immunity and tolerance: Genetic footprint of natural selection in the transcriptional regulatory region of HLA-G

AuthorsGineau, L.; Luisi, Pierre ; Laayouni, Hafid ; Sabbagh, Audrey
Issue Date2015
PublisherNature Publishing Group
CitationGenes and Immunity 16: 57-70 (2015)
Abstract© 2015 Macmillan Publishers Limited. Human leukocyte antigen-G (HLA-G) has well-recognized immunosuppressive properties modulating the activity of many immune system cells, and polymorphisms observed at the HLA-G 5′ upstream regulatory region (5′URR) may influence gene transcriptional regulation. In this study, we characterized the sequence variation and haplotype structure of the HLA-G 5′URR in worldwide populations to investigate the evolutionary history of the HLA-G promoter and shed some light into the mechanisms that may underlie HLA-G expression control. A 1.4-kb region, encompassing the known HLA-G regulatory elements, was sequenced in three African populations from Senegal, Benin and Congo, and data were combined with those available in the literature, resulting in a total of 1411 individuals from 21 worldwide populations. High levels of nucleotide and haplotype diversities, excess of intermediate-frequency variants and reduced population differentiation were observed at this locus when compared with the background genomic variation. These features support a strong molecular signature of balancing selection at HLA-G 5′URR, probably as a result of the competing needs to maintain both a maternal-fetal immune tolerance and an efficient host immune response to invading pathogens during human evolution. An extended analysis of a 300-kb region surrounding HLA-G revealed that this region is not involved in a hitchhiking effect and may be the direct target of selection.
DescriptionGineau, L. et al.
Publisher version (URL)http://dx.doi.org/10.1038/gene.2014.63
URIhttp://hdl.handle.net/10261/111610
DOI10.1038/gene.2014.63
Identifiersdoi: 10.1038/gene.2014.63
e-issn: 1476-5470
issn: 1466-4879
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