title: A comprehensive study of polymorphic sites along the HLA-G gene: implication for gene regulation and evolution.
abstract: HLA-G molecule plays an important role on immune response regulation and has been implicated on the inhibition of T and natural killer cell cytolytic function and inhibition of allogeneic T-cell proliferation. Due to its immune-modulator properties, the HLA-G gene expression has been associated with the outcome of allograft and of autoimmune, infectious, and malignant disorders. Several lines of evidence indicate that HLA-G polymorphisms at the 5'-upstream regulatory region (5' URR) and 3'-untranslated region (3' UTR) may influence the HLA-G expression levels. Because Brazilians represent one of the most heterogeneous populations in the world with the widest HLA-G coding region variability already detected among the studied populations, a high level of variability and haplotype diversity would be expected in Brazilians. On this basis, the 5' URR, coding, and 3' UTR variability were evaluated in a Brazilian series consisting of 100 healthy bone marrow donors, as well as the linkage disequilibrium pattern along the gene and the extended haplotypes encompassing several gene segment variations. The HLA-G locus seems to present six different HLA-G lineages showing functional variations mainly in nucleotides of the regulatory regions. Differences were observed at the 5' URR in positions that either coincide with or are close to transcription factor-binding sites and at the 3' UTR mainly in positions that have already been reported to influence HLA-G mRNA availability. We report several lines of evidence for balancing selection acting on the regulatory regions, which may indicate that these HLA-G lineages may be related to the differential HLA-G expression profiles.
authors.affiliation: Laboratório de Genética Molecular e Citogenética, Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Brasil. erick.castelli@gmail.com
authors.forename: Erick C
authors.initials: EC
authors.lastname: Castelli
authors.forename: Celso T
authors.initials: CT
authors.lastname: Mendes-Junior
authors.forename: Luciana C
authors.initials: LC
authors.lastname: Veiga-Castelli
authors.forename: Michel
authors.initials: M
authors.lastname: Roger
authors.forename: Philippe
authors.initials: P
authors.lastname: Moreau
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Donadi
mesh_terms: D001483:Base Sequence; D001938:Brazil; D017931:DNA Primers / Q000235:genetics; D019143:Evolution, Molecular; D005786:Gene Expression Regulation / Q000235:genetics*; D014644:Genetic Variation; D059951:HLA-G Antigens / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D012641:Selection, Genetic; D017422:Sequence Analysis, DNA
chemical_list: D017931:DNA Primers; D059951:HLA-G Antigens