Distributions of the HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 alleles and haplotype frequencies of 1763 stem cell donors in the Colombian Bone Marrow Registry typed by next-generation sequencing

The HLA compatibility continues to be the main limitation when finding compatible donors, especially if an identical match is not found within the patient's family group. The creation of bone marrow registries allowed a therapeutic option by identifying 10/10 compatible unrelated donors (URD). However, the availability and frequency of haplotypes and HLA alleles are different among ethnic groups and geographical areas, increasing the difficulty of finding identical matches in international registries. In this study, the HLA-A, -B, -C, -DRB1, and -DQB1 loci of 1763 donors registered in the Colombian Bone Marrow Registry were typed by next-generation sequencing. A total of 52 HLA-A, 111 HLA-B, 41 HLA-C, 47 HLA-DRB1, and 20 HLA-DQB1 alleles were identified. The 3 most frequent alleles for each loci were A*24:02g (20,8%), A*02:01g (16,1%), A*01:01g (7.06%); B*35:43g (7.69%), B*40:02g (7.18%), B*44:03g (6.07%); C*04:01g (15.40%), C*01:02g (10.49%), C*07:02g (10.44%); DRB1*04:07g (11.03%), DRB1*07:01g (9.78%), DRB1*08:02g (6.72%); DQB1*03:02g (20.96%), DQB1*03:01g (17.78%) and DQB1*02:01g (16.05%). A total of 497 HLA-A-C-B-DRB1-DQB1 haplotypes were observed with a frequency greater than or equal to 0.05% (> 0.05%); the haplotypes with the highest frequency were A*24:02g similar to B*35:43g similar to C*01:02g similar to DQB1*03:02g similar to DRB1*04:07g (3.34%), A*29:02g similar to B*44:03g similar to C*16:01g similar to DQB1*02:01g similar to DRB1*07:01g (2.04%), and A*01:01g similar to B*08:01g similar to C*07:01g similar to DQB1*02:01g similar to DRB1*03:01g (1.83%). This data will allow the new Colombian Bone Marrow Donor Registry to assess the genetic heterogeneity of the Colombian population and serve as a tool of interest for future searches of unrelated donors in the country.

Automated summary

The main limitation in finding compatible donors is the HLA compatibility, especially if no identical match is found within the patient's family group. Bone marrow registries have allowed the identification of 10/10 compatible unrelated donors, but the availability and frequency of haplotypes and HLA alleles vary among ethnic groups and geographical areas, making it difficult to find identical matches in international registries.