%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Gineau, Laure
%A Luisi, P.
%A Castelli, E. C.
%A Milet, Jacqueline
%A Courtin, David
%A Cagnin, N.
%A Patillon, B.
%A Laayouni, H.
%A Moreau, P.
%A Donadi, E. A.
%A Garcia, André
%A Sabbagh, A.
%T Balancing immunity and tolerance : genetic footprint of natural selection in the transcriptional regulatory region of HLA-G
%D 2015
%L fdi:010063915
%G ENG
%J Genes and Immunity
%@ 1466-4879
%K SENEGAL ; BENIN ; CONGO
%M ISI:000348358100008
%N 1
%P 57-70
%R 10.1038/gene.2014.63
%U https://www.documentation.ird.fr/hor/fdi:010063915
%> https://www.documentation.ird.fr/intranet/publi/2015/03/010063915.pdf
%V 16
%W Horizon (IRD)
%X 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.
%$ 050 ; 020