Novel HLA-alleles identified in populations of the Northern Caucasus
1 The Rosplasma Center of Medical Research & Industry, Kirov, Russia
2 Kirov Research Institute of Hematology and Blood Transfusion, Киров, Россия
E-mail: loginova-ma@rosplasma.ru
Accepted 20 September 2016
Summary
Objective
A study in genetic diversity of HLA alleles in populations of the Northern Caucasus.
Materials and Methods
High-resolution HLA typing of A, B, C, DRB1 and DQB1 loci was carried out by means of Sanger sequencing technique for 2,543 DNA samples from potential donors of hematopoietic stem cells, recruited in the Republics of Dagestan and Chechnya. To confirm and describe the new alleles, we used new pyrosequencing technologies (Roshe), next-generation sequencing (NGS, GenDx), and monoallelic sequencing (PROTRANS).
Results and Discussion
In the course of this study, we identified 15 new HLA alleles. Frequency of the new alleles in population is approximately 1: 170. The North Caucasian Republics are characterized by maximal frequency of new alleles among all the studied Russian populations, since these ethnic communities are underrepresented in bone marrow donor registries. This is related to the genetic profile of these populations. It should be noted that the 12 newly identified alleles are characterized by nucleotide substitutions which result into amino acid substitutions in domains constituting the peptide binding groove of HLA molecules, thus being involved into the “friend-or-foe” recognition. According to recent data, as by July 31, 2016, the nine novel alleles were registered by the WHO Nomenclature Committee for Factors of the HLA System: 3 HLA-loci A, 2 HLA-loci B, 1 HLA-loci C, 2 HLA-loci DRB1, 1 HLA loci DQB1. Interestingly, some of these alleles were identified in several non-related persons, i.e., A*26:106, B*57:78, A*24:314 were identified in two, five and seventeen cases correspondingly. This result suggests a turnover of these alleles in Russian population rather, than random genetic mutations. At present time, our laboratory is unable to identify specific allele differences for other 6 alleles as compared with known alleles.
Conclusion
The studies performed have shown relevance of further research in HLA-allele diversity among different Russian populations. A regional prevalence of HLA traits among potential HSC donors would increase efficiency of their matching to the patients at Russian clinics performing allogeneic stem cell transplantation.
Keywords
Hla-typing, northern caucasus, new alleles, genetic diversity
Accepted 20 September 2016