ABSTRACT
HLA allele matching is critical to successful bone marrow transplantation between a patient and donor. Non-functional HLA alleles, so called 'null alleles', are not well described within a large population of well HLA-typed ethnically diverse individuals despite their impact on donor selection. A retrospective analysis was performed on 833,789 unrelated donors (URDs) in the National Marrow Donor Program's Be The Match Registry® typed for HLA-A, -B, -C, -DRB1, -DQB1, and -DPB1 by next-generation DNA sequencing. Results showed that null alleles occur in low frequency (2.30E-04) compared to expressed alleles. Their overall frequency ranged from 6.00E-07 to 9.25E-04 with a median of 1.20E-06. The expected allele associations were commonly observed for HLA-A*24:09N, HLA-B*51:11N, and HLA-C*04:09N; however, associations outside of the expected were also observed. Notably, 82% of the National Marrow Donor Program Registry URDs carrying HLA-A*24:11N showed a different HLA-C allele association, HLA-C*05:01, compared to the allele described by prior published work characterizing German donor populations, HLA-C*04:01. The frequencies of these observed null alleles and linkage disequilibrium information could be invaluable and helpful in guiding the HLA testing decisions.
Subject(s)
Alleles , Bone Marrow/immunology , Gene Frequency , HLA Antigens/genetics , Haplotypes , Registries , Unrelated Donors , Bone Marrow Transplantation , Ethnicity/genetics , Exons , High-Throughput Nucleotide Sequencing/methods , Histocompatibility Antigens Class I/genetics , Histocompatibility Antigens Class II/genetics , Histocompatibility Testing/methods , Humans , Linkage Disequilibrium , Mutation , Retrospective Studies , Sequence Analysis, DNA/methodsABSTRACT
The search for a suitable human leukocyte antigen (HLA)-matched unrelated adult stem cell donor (URD) or umbilical cord blood unit (UCB) is a complex process. The National Marrow Donor Program (NMDP) developed a search algorithm known as HapLogic, which is currently provided within the NMDP Traxis application. The HapLogic algorithm has been in use since 2006 and has advanced URD/UCB HLA-matching technology. The algorithm has been shown to have high predictive accuracy, which can streamline URD/UCB selection and drive efficiencies in the search process to the benefit of the stem cell transplantation community. Here, we describe the fundamental components of the NMDP matching algorithm, output, validation, and future directions.
