DRB-DQB1 DIVERSITY IN THE ANALYSIS OF 4727 DONORS TYPED BY SBT.

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DRB-DQB1 DIVERSITY IN THE ANALYSIS OF 4727 DONORS TYPED BY SBT.
Laura Burdett PhD , Kirstin Smith , Bin Tu , Martin Guiterrez , Kelly Buck , Martin Maiers , Jennifer Ng PhD , Carolyn Hurley PhD , Robert Hartzman MD and Marcelo Fernandez-Vina PhD . Kensington MD, Georgetown Univ/Navy, 20895, CW Bill Young DoD Marrow Donor Program and Minneapolis MN, NMDP .

Diversity is characteristic of the HLA system. In this study 4727 potential BMT donors from 5 ethnic groups were typed for DRB1/3/4/5 loci by SBT and for DQB1 by RLS. Even though the panel analyzed here may be skewed by the occurrence of rare patient’s HLA genotypes important information about linkage disequilibrium patterns may be gained. Haplotype assignments were done by examining previously known associations and by applying the EM algorithm; both procedures yielded identical results. We observed 71 DRB1 alleles - 46 were typed in at least 5 subjects accounting for 99.5 percent of the alleles. Analysis of the 3 loci haplotypes showed 157 haplotypes that were found in at least two instances each (99.1 percent); 25 haplotypes had unique alleles and 59 corresponded to unique arrays of alleles. In spite of the finding of conserved haplotype blocks we could identify at least 2 haplotypes for each DRB1 allele that was observed more than 17 times. The strength of specific associations varied in different ethnicities. DRB5*01011 associates almost absolutely with DRB1*15011 in all ethnic groups and with DRB1*1503 in African subjects however we observed this allele associated with various DRB1*15/16 alleles in Asians. We observed almost absolute associations between DRB1*13021 and DRB3*03011, and DRB1*13011 with DRB3* 0101 or 0202 in all populations with exception of Africans in which DRB1-DRB3 exceptions were more frequent (10 percent). The present study demonstrates that less than 60 DRB1 alleles account for more than 99 percent of the gene pool of all populations combined; in spite of this conservation we observed multiple DRB-DQ haplotypes for almost all common DRB1 alleles.