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.

HLA等位基因匹配对于患者和供体之间的成功骨髓移植至关重要。非功能性HLA等位基因，即所谓的“无效等位基因”，尽管对捐献者的选择有影响，但在大量HLA类型良好的种族多样化个体中并未得到很好的描述。通过下一代DNA测序对国家骨髓捐献者计划的Be The MatchRegistry®中的833,789个无关捐献者（URD）进行了回顾性分析，该人为HLA-A，-B，-C，-DRB1，-DQB1和-DPB1类型。 。结果表明，与表达的等位基因相比，无效等位基因在低频（2.30E-0）中发生。它们的总频率范围从6.00E-07到9.25E-03，中位数为1.20E-06。通常在HLA-A * 24：09N，HLA-B * 51：11N和HLA-C * 04：09N中观察到预期的等位基因关联；然而，还观察到超出预期的关联。值得注意的是，与先前发表的表征德国捐赠人群特征的等位基因相比，携带HLA-A * 24：11N的国家骨髓捐赠者计划注册表URD显示出不同的HLA-C等位基因关联，即HLA-C * 05：01。 ，HLA-C * 04：01。这些观察到的无效等位基因和连锁不平衡信息的频率可能是无价的，有助于指导HLA测试决策。