HLA‐DPB1 DNA POLYMORPHISM IN THE SWISS POPULATION: LINKAGE DISEQUILIBRIUM WITH OTHER HLA LOCI AND POPULATION GENETIC AFFINITIES

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Abstract
Allelic diversity at the HLA‐DPB1 locus was determined by PCR‐oligotyping in a sample of 125 healthy Swiss individuals. A total of 17 alleles were detected among which four main alleles (DPB 1*0401, *0201, *0301, *0402) reached a cumulative frequency of 74.8%. HLA‐A and ‐B (by serology) and HLA‐DRB1 (by oligotyping) allelic polymorphisms were analysed also. HLA‐B and HLA‐DRB1 loci were highly polymorphic with 25 and 28 alleles respectively and similar heterozygosity levels of 0.93 and 0.92. These two loci were found to be more polymorphic than expected under neutrality, while lower heterozygosity levels were found for HLA‐A (0.87) and DPB1 (0.81) loci. This paper presents also a global comparison of DPB1 allelic frequencies among 15 populations from four continents. As opposed to the DRB1 locus, overall DPB1 is shown to have a lower level of polymorphism and may be considered as neutral in all tested populations. DPB 1 genetic diversity is correlated significantly with geography also, as found previously for DRB1. Two‐ and four‐locus haplotype frequencies were determined and the significance of their linkage disequilibrium tested by an original non‐parametric method. A significant positive linkage disequilibrium was found for 11 A‐B, 16 B‐DRB1, 7 DRB1‐DPB1 and 3 A‐B‐DRB1‐DPB1 haplotypes. The overall linkage disequilibrium between DRB1 and DPB1 was much lower than expected from the physical distance and lower than for A‐B and B‐DRB1 pairs. The implications of these results for bone marrow transplantation and for the evolution of HLA loci are discussed.