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HAPLOTYPE REFERENCE STANDARDS FOR HLA DR-DQ AND B-C IN EUROPEAN AMERICANS: SUPERIOR TYPING ASSIGNMENT AND INFERENCE ALONG WITH NEW POPULATION GENETICS KNOWLEDGE.
William Klitz , Martin Maiers , Stephen Spellman , Lee Ann Baxter-Lowe , Berbara Schmeckpeper , Thomas M. Williams and Marcelo Fernandez-Vina . Oakland CA, Children
s Hospital Oakland Research Institute, 94609, Childrens Hospital Oakland Research Institute ; Minneapolis MN, National Marrow Donor Program ; San Francisco CA, University of California ; Baltimore MD, American Red Cross ; Albuquerque NM, University of New Mexico, Health Sciences Center and Washington DC, Georgetown University .
A National Marrow Donor Program® sponsored collaborative study typed 1,899 unrelated European American stem cell donors at the allele level for the HLA DRB1, DQA1, DQB1, C and B loci. The intensive typing validation measures employed makes the accuracy of haplotype composition and haplotype frequencies exceptionally high. The haplotype frequencies have immediate application to HLA typing and allogeneic transplantation. The sets of DR/DQ and B/C loci are especially valuable for HLA typing and unrelated donor selection because of their high linkage disequilibrium. The 3,798 haplotypes yielded a total of 75 DRB1-DQA1-DQB1 and 162 B-C distinct haplotypes. The frequency distribution of both the DR-DQ and B-C haplotypes were strongly right skewed with rare haplotypes (occurring at a frequency of less than 1%) constituting 79% and 91% of the distinct DR/DQ and B/C haplotypes. This data permits the accurate assignment of the alleles for the less polymorphic locus within tightly linked sets of loci: given either DRB1 or B typing, it was possible to infer the exact DQA1 and DQB1 or C composition of a haplotype with high confidence. The 36 observed DQA1-DQB1 haplotypes conformed to the known pattern of permissible heterodimers. The haplotype frequency tables provide a reference standard for HLA typing of the DR/DQ and B/C loci in European Americans, suitable as an aid to typing of this ethnic group, as well as for the selection of potential donors in stem cell transplantation.