Maintaining updated DNA-based HLA assignments in the National Marrow Donor Program bone marrow registry

The National Marrow Donor Program (NMDP®) has instituted an approach to address the impact of new alleles on the DNA-based HLA assignments obtained during volunteer donor typing. This approach was applied to the DRB typing results from 371 187 donors received from 14 laboratories in 1999. Samples were tested with a standardized set of sequence specific oligonucleotide reagents and the positive and negative hybridization results transmitted electronically to the NMDP. A software program interpreted the primary data into HLA assignments and rejected assignments which did not produce a result at the specified level of resolution. Comparison of the HLA assignments derived by the NMDP software to the assignments made by the laboratories using several local software programs showed 90.5% of the assignments to be identical. Differences in assignments were explained by varying levels of typing resolution, variation in the inclusion of the second expressed DRB loci, disparity arising when alternative assignments were summarized, and failure to submit correct information. When the primary data collected in 1999 were interpreted into HLA assignments using the set of alleles defined in July 2000, 74% of the HLA-DRB assignments were altered by the description of new alleles, justifying the development of this software.