The genetic structure of 3'untranslated region of the HLA-G gene: polymorphisms and haplotypes.
The HLA-G gene is predominantly expressed at the maternal-fetal interface. It has been associated with maternal-fetal tolerance and in the inhibition of cytotoxic T lymphocyte and natural killer cytolytic functions. At least two variations in the 3'untranslated region (UTR) of HLA-G locus are associated with HLA-G expression levels, the 14-bp deletion/insertion polymorphism and the +3142 single-nucleotide polymorphism (SNP). However, this region has not been completely characterized yet. The variability of the 3'UTR of HLA-G gene and its haplotype structure were characterized in 155 individuals from Brazil, as well as HLA-G alleles associated with each of the 3'UTR haplotype. The following eight variation sites were detected: the 14-bp polymorphism and SNPs at the positions +3003T/C, +3010C/G, +3027A/C, +3035C/T, +3142G/C, +3187A/G and +3196C/G. Similarly, 11 different 3'UTR haplotypes were identified and several HLA-G alleles presented only one 3'UTR haplotype. In addition, a high linkage disequilibrium among the variation sites was detected, especially among the 14-bp insertion and the alleles +3142G and +3187A, all previously associated with low mRNA availability, demonstrating that their effects are not independent. The detailed analyses of 3'UTR of the HLA-G locus may shed some light into mechanisms underlying the regulation of HLA-G expression.
Divisão de Imunologia Clínica, Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Av. Bandeirantes 3900, Ribeirão Preto, São Paulo, Brazil. erick.castelli@gmail.com
E C
EC
Castelli
C T
CT
Mendes-Junior
N H S
NH
Deghaide
R S
RS
de Albuquerque
Y C N
YC
Muniz
R T
RT
Simões
E D
ED
Carosella
P
P
Moreau
E A
EA
Donadi
D020413:3' Untranslated Regions; D000328:Adult; D000483:Alleles; D001938:Brazil; D005260:Female; D040342:Genetic Structures; D006680:HLA Antigens / Q000235:genetics*; D059951:HLA-G Antigens; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion
D020413:3' Untranslated Regions; D006680:HLA Antigens; D059951:HLA-G Antigens; D015395:Histocompatibility Antigens Class I