A putative susceptibility locus on chromosome 18 is not a major contributor to human selective IgA deficiency: evidence from meiotic mapping of 83 multiple-case families

J Immunol. 1999 Aug 15;163(4):2236-42.


Previous reports of an association between constitutional chromosome 18 abnormalities and low levels of IgA suggested that this chromosome contains a susceptibility locus for selective IgA deficiency (IgAD), the most frequent Ig deficiency in humans. IgAD is genetically related to common variable immunodeficiency (CVID), characterized by a lack of additional isotypes. Our previous linkage analysis of 83 multiple-case IgAD/CVID families containing 449 informative pedigree members showed a significantly increased allele sharing in the chromosome region 6p21 consistent with allelic associations in family-based and case-control studies and provided the evidence for a predisposing locus, termed IGAD1, in the proximal part of the MHC. We have typed the same family material at 17 chromosome 18 marker loci with the average intermarker distance of 7 cM. A total of 7633 genotypes were analyzed in a nonparametric linkage analysis, but none of the marker loci exhibited a significantly increased allele sharing in affected family members. In addition, reverse painting and deletion mapping of a panel of constitutional chromosome 18 deletions/translocations showed the presence of IgA-deficient and IgA-proficient patients with the same abnormality and did not reveal a region commonly deleted. The linkage analysis of chromosome 8 and 21 regions involved in reciprocal translocations t(8;18) and t(18;21), which were identified in two patients lacking IgA, did not disclose a significant allele sharing. Although these results do not exclude the presence of a minor predisposing locus on this chromosome, such a putative locus would confer a population risk of developing IgAD/CVID much lower than IGAD1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Case-Control Studies
  • Chromosome Aberrations / blood
  • Chromosome Aberrations / genetics
  • Chromosome Aberrations / immunology
  • Chromosome Disorders
  • Chromosome Mapping
  • Chromosomes, Human, Pair 18 / genetics*
  • Chromosomes, Human, Pair 18 / immunology
  • Female
  • Gene Deletion
  • Genetic Linkage / immunology
  • Genetic Markers
  • Genetic Predisposition to Disease / immunology*
  • Humans
  • IgA Deficiency / blood
  • IgA Deficiency / genetics*
  • Immunoglobulin A / blood
  • Male
  • Meiosis / genetics*
  • Meiosis / immunology
  • Translocation, Genetic / immunology


  • Genetic Markers
  • Immunoglobulin A