The molecular genetics of HLA-related disorders

The HLA region on the short arm of chromosome 6 contains a set of highly polymorphic loci responsible for regulating the immune response. Particular haplotypes, defined serologically, have been associated with a risk of developing certain autoimmune diseases such as insulin-dependent (juvenile-onset) diabetes mellitus, multiple sclerosis and rheumatoid arthritis. Recent developments in molecular biology have permitted an improved resolution of the locus and of the sequential arrangement of the susceptibility determinants on these haplotypes. Restriction fragment length polymorphisms have allowed subdivisions of serological haplotypes to be made. These correlate with disease susceptibility in some cases. Amplification of specific HLA class II alleles and nucleic acid sequencing have resulted in the identification of the structural determinants in the HLA that underlie some of these diseases.