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HAPLOTYPE REFERENCE STANDARDS FOR THE HLA SYSTEM IN EUROPEAN AMERICANS.
W. Klitz, M. Maiers, L. Gragert, S. Spellman, B. Schmeckpeper, T. M. Williams and M. Fernandez-Vina. Berkeley CA, Univ California, Public Health; Minneapolis MN, National Marrow Donor Program; Baltimore MD, American University; Albuquerque NM, Univ New Mexico and Washington DC, Georgetown University.

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A National Marrow Donor Program® collaborative study typed 1,899 unrelated European American stem cell donors at the allele level for the 11 expressed human histocompatibility loci, including HLA A, C, B, DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1 and DPB1. The typing validation measures employed makes the accuracy of haplotype composition and haplotype frequencies exceptionally high. A report on DRB1-DQA1-DQB1 haplotypes, identifying a discrete set of 75 haplotypes in this population, is completed (Klitz et al. 2003). We now describe results for the entire HLA complex. Inclusion of the rather sparse polymorphism at DRB3, DRB4 and DRB5 increased the number of haplotypes in the DR-DQ region by 15%. A total of 144 distinct B-C haplotypes and 40 DPA1-DPB1 haplotypes were identified. No pattern of allelic restriction, as seen in DQ was evident in DP heterodimers. Given high resolution typing of the most highly polymorphic member (DRB1, DPB1 and B) of each group of tightly linked loci (DR-DQ, DP and C-B), it was shown that the inference of alleles at untyped loci in a haplotype was feasible. Disequilibrium between the tightly linked clusters of loci, while still measurable, dropped rapidly. For the region as a whole, extending from HLA A to HLA DPB1, few haplotypes held together by disequilibrium were present. The haplotype frequency tables provide a reference standard for HLA typing in European Americans, suitable as an aid to typing this ethnic group, as well as for the selection of potential donors in stem cell transplantation. Funding support from the Office of Naval Research.