Molecular analysis of the MHC class II region in DR4, DR7, and DR9 haplotypes.
Within the class II region of the major histocompatibility complex (MHC) the amount of DNA in the DR-DQ interval has been shown to be haplotype dependent, with those carrying the DR4, DR7, and DR9 specificities having been reported to contain 110-160 kilobases (kb) more DNA than haplotypes carrying the DR3 specificity. Certain subtypes of haplotypes carrying particular DR specificities are more closely associated with autoimmune diseases than others. With the prospect of the DNA perhaps containing a disease susceptibility locus, we have mapped eight DR4 and two DR7 homozygous cell lines and a DR7/9 heterozygous cell line together with a control DR3 cell line using pulsed field gel electrophoresis (PFGE) with the enzymes Bss H II, Pvu I, and Not I/Nru I. Our results, however, show that the presence and amount of the extra DNA is constant irrespective of the subtype. We have also tried to narrow down the position of insertion of the extra DNA using eight further rare-cutting enzymes but, due to the polymorphic nature of sites and/or differences in methylation in this region, it was not possible to refine it further than between DRA and DQA1/B1. This polymorphic nature of the DR-DQ region is unusual, considering the uniformity of rare cutter sites that has been observed within the rest of the class II, and class III, regions. The presence of this, and other, haplotype dependent variations in the DNA content of the DR subregion may be important with respect to recombination and will be particularly interesting if the additional DNA is found to contain novel genes.
Department of Biochemistry, Oxford University, UK.
E
E
Kendall
J A
JA
Todd
R D
RD
Campbell
D002460:Cell Line; D004247:DNA / Q000032:analysis; D015342:DNA Probes; D016521:Electrophoresis, Gel, Pulsed-Field; D005802:Genes, MHC Class II / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen / Q000235:genetics; D015809:HLA-DR7 Antigen / Q000235:genetics; D006239:Haplotypes; D006801:Humans; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D015183:Restriction Mapping
D015342:DNA Probes; D006684:HLA-DR Antigens; D059810:HLA-DR Serological Subtypes; D015804:HLA-DR4 Antigen; D015809:HLA-DR7 Antigen; C038988:HLA-DR9 antigen; D004247:DNA