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
| Autor: | Vorechovsky, I., Blennow, E., Magnus Nordenskjöld, Webster, Adb, Hammarstrom, L. |
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| Rok vydání: | 1999 |
| Předmět: |
Chromosome Aberrations
Genetic Markers Male Genetic Linkage Immunology IgA Deficiency Chromosome Mapping Chromosome Disorders Translocation Genetic Immunoglobulin A Meiosis Case-Control Studies Immunology and Allergy Humans Female Genetic Predisposition to Disease Chromosomes Human Pair 18 Gene Deletion |
| Zdroj: | Europe PubMed Central Karolinska Institutet |
| ISSN: | 0022-1767 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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