Mapping of a restriction fragment length polymorphism associated with defective DR beta 4 chain expression to the HLA-DRB1 gene

The HLA-DR beta 4 chain, encoded by the DRB4 gene, carries two DRw53 determinants normally expressed by DR4, DR7, and DR9 individuals. However, some DR7 individuals (DR7, Dw11) fail to express the DR beta 4 chain. At the genomic level, a HindIII restriction fragment length polymorphism can be detected in these individuals with a DR beta cDNA probe. The association of this altered HindIII fragment with defective beta 4 chain expression suggested the possibility that the polymorphic fragment was derived from the DRB4 gene and might, therefore, be related to the defect in expression. However, detailed Southern blot analysis has now mapped the polymorphic fragment to the 3' end of the DRB1 gene, approximately 100 kb away from the defective DRB4 gene. Although the alteration in the DRB1 gene might involve sequences important in regulating the expression of the DRB4 gene, it is more likely that the association results from strong positive linkage disequilibrium between these DR beta chain genes.