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Polymorphism of the human α1 immunoglobulin gene 3′ enhancer hs1,2 and its relation to gene expression
Author(s) -
Denizot Yves,
Pinaud Eric,
Aupetit Corinne,
Le Morvan Caroline,
Magnoux Emmanuelle,
Aldigier Jean Claude,
Cogné Michel
Publication year - 2001
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2001.01217.x
Subject(s) - minisatellite , biology , allele , enhancer , genetics , locus (genetics) , gene , microbiology and biotechnology , tandem repeat , variable number tandem repeat , southern blot , genotype , gene expression , microsatellite , genome
Summary We studied the hs1,2 transcriptional enhancer identified downstream of the human α1 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’α1A, α1B and α1C (including one, two and three repeats, respectively). Five different α1 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 α1 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′α1 region. In conclusion, the present study further demonstrates the genetic instability of the 3′α 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 α1 gene could play a role in the outcome of diseases involving immunoglobulin secretion.