1013-lbp: identification of 2127 new HLA alleles in potential donors registered with DKMS donor centers in Germany, the United States and Poland

Abstract

We describe 2127 new HLA alleles: 598 HLA-A, 755 HLA-B and 774 HLA-C alleles, accounting for 28.9 % of the currently known HLA class I alleles. Buccal swabs or blood samples of newly recruited donors from three national DKMS donor centers were typed for HLA using sequencing-based typing (SBT) at the ASHI-accredited laboratory of HistoGenetics (Ossining, NY). New HLA class I alleles were identified after determination of DNA sequences of HLA exons 2 and 3. Comparison of the new allele sequences and their most homologous counterpart lead to detection and description of nucleotide variations in DNA sequences. Self-assessed parentage of individuals carrying new HLA class I alleles were examined. Of the 2127 new HLA class I alleles described, 1336 (62.8%) were observed in donors from Germany, 422 (19.8%) in US donors, 213 (10.0%) in donors from Poland, and 156 (7.3%) new alleles were found in donors from at least two countries. We identified new alleles in 57 allele groups, including 192 C ∗ 07, 144 A ∗ 02 and 112 C ∗ 03 alleles, The majority (93.8%) of the new alleles corresponded to single nucleotide variations. 67.0% of the new alleles comprised non-synonymous nucleotide substitutions and 30.0% silent mutations. The remaining 3.0% showed nonsense mutations identified in null alleles. New alleles were found disproportionally often in minority donors. Further, 527 new alleles (24.8%) were identified in multiple individuals. We described 2127 new HLA class I alleles that have been identified in upfront HLA typing of newly registered DKMS stem cell donors. The occurrence of many new alleles in multiple individuals who originated partly from different populations indicates that newly identified alleles are not necessarily rare and thus may be of relevance for actual stem cell donor searches.