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ANALYSIS OF NEW, VERY RARE AND RARE HLA ALLELES AMONG VOLUNTEER HEMATOPOIETIC STEM CELL DONORS IN CROATIAN BONE MARROW DONOR REGISTRY

The Croatian Bone Marrow Donor Registry (CBMDR) with more than 50, 000 registered volunteer hematopoietic stem cell donors provides a large dataset for studying HLA allele polymorphism in the Croatian population which in a certain number of cases leads to the identification of new, rare and very rare HLA alleles. During the last two years we have identified two new HLA alleles and a number of very rare or rare HLA alleles by sequence based typing (SBT) method using Olerup SBT kits and Assign SBT software for the analysis. The first new allele reported in 2016 was HLA-A*01:200 which differs from HLA-A*01:12 in four nucleotide transitions in exon 3 leading to three- amino acid substitution in codons 65, 75 and 76. The allele was confirmed in two siblings, volunteer donors from CBMDR originating from different part of Croatia (north- west) than the donor in which it was identified for the first time (middle Dalmatia) and analysis revealed that all three individuals carry the haplotype: HLA- A*01:200~B*08:01~C*07:01~ DRB1*03:01 ~DQB1*02:01~DPB1*01:01. The second new allele has been officially assigned by the WHO Nomenclature Committee in December 2017 and the given sequence name HLA-B*18:37:02. The new allele differs from HLA-B*18:37 in one change in exon 2 at nt 161 resulting in a non-coding change in codon 53. Applying the Rare Allele Detector tool incorporated to the Allele Frequency Net Database (AFND) website, four alleles found were determined as very rare: HLA-B*08:78, HLA- B*18:103, HLA-DRB1*11:04:06 and HLA-DRB1*12:39. The HLA-A*24:41, HLA-B*07:02:28, HLA-B*35:03:03, HLAB* 35:101:01, HLA-B*39:40:01N, HLA-B*44:16, HLA-B*51:78, HLA-DRB1*01:31, HLA-DRB1*13:23:01, HLA-DRB1*14:111 and HLA-DRB1*16:01:08 were classified as rare alleles. All this data complements the knowledge about the HLA polymorphisms of the Croatian population, provides a foundation for further studies in population genetics and highlights once again the importance of recruiting donors from different populations.

new, rare and very rare HLA HLA alleles, CBMDR

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