LINKAGE ANALYSES TO ASSIGN THE LOCUS FOR AUTOIMMUNE POLYGLANDULAR DISEASE TYPE I

Abstract

The autoimmune phenomena associated with many human diseases are still only partially understood. Unravelling the molecular palhogenesis of inherited diseases with a strong autoimmune component in their clinical expression could help to dissect the molecular background of abnormal immune response. One such genetic disorder is autosomal resessive autoimmune polyglandular disease type I (PGD I), also known as autoimmune polyendocrinopathy-candidiasis - ectodermal dystrophy (APECED, MIM 240300). This disease is especially enriched in the genetically isolated population of Finland. Here we have taken advantage of newly developed amplifiable multiallelic microsatellite markers coupled with the microtiter well format of the polymerase chain reaction and linkage analyses to establish the most probable chromosomal location for the APECED locus. The rapid “semiautomated” protocol was here aplied to analyze 100 chromosomally assigned polymorphic loci. The method proved to be an effective and economical tool for gene mapping compared with standard blotting and hybridization and resulted in the preliminary assignment of the APECED locus.