Alu Repeats and Evolution of the HLA-DQA1 Locus
The HLA-DQA1 gene is highly polymorphic in the coding as well as in the non-coding regions. Analysis of polymorphisms at the DNA level by use of restriction enzymes shows that multiple restriction sites are simultaneously affected, thus suggesting that insertion/deletion mechanisms might be in part responsible for the generation of genetic variability at this locus. To study in detail this phenomenon we have cloned and sequenced DNA fragments derived from the HLA-DQA1 locus isolated from different haplotypes. This work has provided clues concerning DNA polymorphisms located in the 5′ flanking region of the gene. Generation of polymorphism seems to be related to the presence of a cluster of repetitive elements of the Alu family; the possible influence of polymorphisms of the regulatory region on the control of gene activity is discussed. Furthermore, we report indications that Alu repeats can be used as tags to study the divergence of HLA-DQA1 and of its alleles from the strictly related HLA-DQA2 gene.
KeywordsRepetitive Element Schistosomal Antigen Alpha Chain Gene Multiple Restriction Site Short Terminal Repeat
Unable to display preview. Download preview PDF.
- Accolla, R.S. and Guardiola, J.: Regulation of human MHC class II genes. J Immunol Res 1: 191–198, 1989Google Scholar
- Auffray, C., Lillie, J.W., Korman, A.J., Boss, J.M., Frèchin, N., Guillemot, F. Cooper, J., Mulligan, R.C. and Strominger, J.L.: Structure and expression of the HLA-DQA and -DXA genes: interallelic alternate splicing of the HLA-DXA gene using a retroviral vector. Immunogenetics 26: 63–73, 1987PubMedCrossRefGoogle Scholar
- Dom, A., Fehling, J.H., Koch, N., Lemeur, M., Gerlinger, P., Benoist, C. and Mathis, D.: B- cell control region at the 5′ end of a MHC class II gene: sequences and factors. Mol Cell Biol 8: 3975–3987, 1988Google Scholar
- Rogers, J.H.: Origin and evolution of retroposons. Part 2: The structure and evolution of retroposons. Intern Rev Cytol 93: 231–279, 1985Google Scholar
- Safer, J.D. and Thurston, S.J.: A negative element with properties similar to those of enhancer is contained within an Alu sequence. Mol Cell Biol 9: 355–364, 1990Google Scholar
- Sasazuchi, T.: Immunological recognition. Cold Spring Harbor Symp Quant Biol. 54: 69–74, 1989Google Scholar