Molecular Genetics of the HLA System: New Tools for the Study of HLA and Disease

Abstract

Molecular biology provides new tools for the study of HLA associated or linked diseases. Restriction enzymes digest the DNA at specific sequences allowing the detection of fragments of various lengths. Using several enzymes and probes for Class I, Class IIα and Class IIβ, an extensive new polymorphism was defined. Some of these fragments correlated with known HLA-A, -B and -DR specificities.

These fragments constitute new markers for susceptibility or resistance genes of HLA associated diseases. In insulin-dependent diabetes mellitus (IDDM) a fragment βDC, EcoRI 2.2 kb, was found to be absent in the rare DR2 patients. Thus, this band seemed to mark the DR2 diabetes resistant haplotype. Likewise, a βDC PvuII 4.0 kb fragment was decreased in DR3 patients. In multiple sclerosis (MS), a βDC BamHI 12 kb fragment was found to have an increased frequency. Moreover, a βDC EcoRV 23 kb fragment was present in all DR7 patients but present in only half of the DR7 controls.

HLA genotyping can be performed using DNA fragments when the genes are not expressed on the cell surface.