Journal Article

A Comprehensive Study of Polymorphic Sites along the HLA-G Gene: Implication for Gene Regulation and Evolution

Michel, Roger, Mendes-Junior, Celso T, Moreau, Philippe, Castelli, Erick C, Veiga-Castelli, Luciana C, Donadi, Eduardo A

2011

Overview

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.

• Publisher: Oxford University Press
• Subject: 3' Untranslated regions / Binding sites / Bone marrow / Cell proliferation / Gene expression / Gene regulation / Haplotypes / Histocompatibility antigen HLA / Immune response / Immune system / Immunomodulation / Linkage disequilibrium / Lymphocytes T / Natural killer cells / Nucleotides / Population studies / Populations / Regulatory sequences