Denizot Y, Pinaud E, Aupetit C, Le Morvan C, Magnoux E, Aldigier J C, Cogné M
Laboratoire d'Immunologie-UMR CNRS 6101, Faculté de Médecine, Limoges, France.
Immunology. 2001 May;103(1):35-40. doi: 10.1046/j.1365-2567.2001.01217.x.
We studied the hs1,2 transcriptional enhancer identified downstream of the human alpha1 gene of the immunoglobulin H (IgH) locus, for which two different allelic configurations (a and b) were previously reported by Southern blotting. By using a polymerase chain reaction (PCR) method we amplified minisatellites within the hs1,2 core enhancer, with variable numbers of tandem repeats (VNTR) defining three 'PCR alleles' alpha1A, alpha1B and alpha1C (including one, two and three repeats, respectively). Five different alpha1 h1,2 genotypes were encountered in a population of 513 donors, representing 13.8, 34.5, 49.7, 1.3 and 0.6% for the AA, BB, AB, AC and BC genotypes, respectively. Luciferase assays showed that increasing the number of minisatellites increased the transcriptional strength of the alpha1 hs1,2 enhancer. Simultaneous determination of Southern blot alleles and VNTR alleles only showed a partial linkage between both types of polymorphism, altogether defining at least six different allelic forms of the 3'alpha1 region. In conclusion, the present study further demonstrates the genetic instability of the 3'alpha region, for which multiple alleles have been generated through inversions and internal deletions and/or duplications. This study also strengthens the hypothesis that the polymorphism at the IgH 3' regulatory region of the alpha1 gene could play a role in the outcome of diseases involving immunoglobulin secretion.
我们研究了在免疫球蛋白H（IgH）基因座的人类α1基因下游鉴定出的hs1,2转录增强子，此前通过Southern印迹法报道了其两种不同的等位基因构型（a和b）。通过使用聚合酶链反应（PCR）方法，我们扩增了hs1,2核心增强子内的微卫星，其串联重复序列（VNTR）数量可变，定义了三个“PCR等位基因”α1A、α1B和α1C（分别包括一个、两个和三个重复）。在513名供体群体中遇到了五种不同的α1 h1,2基因型，AA、BB、AB、AC和BC基因型分别占13.8%、34.5%、49.7%、1.3%和0.6%。荧光素酶测定表明，增加微卫星数量会增加α1 hs1,2增强子的转录强度。同时测定Southern印迹等位基因和VNTR等位基因仅显示两种多态性之间存在部分连锁，总共定义了3'α1区域的至少六种不同等位基因形式。总之，本研究进一步证明了3'α区域的遗传不稳定性，该区域通过倒位和内部缺失和/或重复产生了多个等位基因。本研究还强化了这样一种假设，即α1基因IgH 3'调控区域的多态性可能在涉及免疫球蛋白分泌的疾病结果中起作用。
