Del Pozzo G, Perfetto C, Ombra M N, Ding G Z, Guardiola J, Maffei A
International Institute of Genetics and Biophysics, Naples, Italy.
Immunogenetics. 1992;35(3):176-82. doi: 10.1007/BF00185111.
The HLA-DQA1 gene exhibits haplotype-specific restriction fragment polymorphisms due to DNA rearrangements. We found that some of these polymorphisms extend into the 5' flanking region of the gene and are distinct from other HLA-DQA1 related DNA polymorphisms so far reported. Sequencing of genomic DNA subclones derived from the 5' flanking region of HLA-DQA1 showed the presence, in a DR4 haplotype, of two repetitive elements of the Alu family, oriented in opposite directions and bracketing an approximately 3 kilobase region immediately adjacent to the promoter of the gene. When DNAs extracted from several cell lines were analyzed by genomic hybridization using single-copy probes relative to these intervening sequences, polymorphisms were observed. No structural alterations of the gene immediately outside the DNA portion delimited by the two Alu elements were observed, thus suggesting that polymorphisms of the 5' end of HLA-DQA1 may be limited to the intervening region between the two Alu repeats. The latter includes upstream regulatory elements controlling the expression of the genes. The possibility that the structure of the DNA in this region may influence the regulation of HLA-DQA1 gene expression in different haplotypes is discussed.
由于DNA重排，HLA - DQA1基因表现出单倍型特异性的限制性片段多态性。我们发现其中一些多态性延伸到该基因的5'侧翼区域，并且与迄今报道的其他HLA - DQA1相关DNA多态性不同。对源自HLA - DQA1基因5'侧翼区域的基因组DNA亚克隆进行测序显示，在DR4单倍型中存在两个Alu家族的重复元件，它们方向相反，将紧邻该基因启动子的一个约3千碱基的区域包围起来。当使用相对于这些间隔序列的单拷贝探针通过基因组杂交分析从几种细胞系中提取的DNA时，观察到了多态性。在由两个Alu元件界定的DNA部分之外，未观察到该基因的结构改变，因此表明HLA - DQA1基因5'端的多态性可能仅限于两个Alu重复序列之间的间隔区域。后者包括控制基因表达的上游调控元件。本文讨论了该区域DNA结构可能影响不同单倍型中HLA - DQA1基因表达调控的可能性。
