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

Autor(es)

Castelli, Erick C. ^[1] ; Mendes-Junior, Celso T. ^[2] ; Veiga-Castelli, Luciana C. ^[3] ; Roger, Michel ^[4] ; Moreau, Philippe ^[5] ; Donadi, Eduardo A. ^[3]

Afiliação do(s) autor(es)

^[1] Univ Fed Goias, Inst Ciencias Biol, Dept Biol Geral, Lab Genet Mol & Citogenet, Goiania, Go - Brazil

^[2] Univ Sao Paulo, Dept Quim, Fac Filosofia Ciencias & Letras Ribeirao Pret, BR-14049 Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo, Dept Clin Med, Fac Med Ribeirao Preto, Div Imunol Clin, BR-14049 Ribeirao Preto, SP - Brazil

^[4] Ctr Hosp Univ Montreal, Dept Microbiol & Immunol, Montreal, PQ - Canada

^[5] Univ Paris 07, Serv Rech Hematoimmunol, Commissariat Energie Atom & Energies Alternat, Inst Univ Hematol, Hop St Louis, DSV, I2BM, Paris - France

• Tipo de documento: Artigo Científico
• Fonte: Molecular Biology and Evolution; v. 28, n. 11, p. 3069-3086, NOV 2011.
• Citações Web of Science: 94

Resumo

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. (AU)

• Processo FAPESP: 07/58420-4 - Polimorfismos da região promotora e expressão de HLA-G em pacientes com histórico de carcinoma de células transicionais da bexiga urinária
• Beneficiário: Erick da Cruz Castelli
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado