Open AccessNext generation sequencing HLA-typing of recipients and donors of allogeneic haematopoietic stem cells
Author(s) -
Е Г Хамаганова,
Alena R Abdrakhimova,
Evgeny A Leonov,
Stanislav P Khizhinskiy,
Т. В. Гапонова,
В Г Савченко
Publication year - 2021
Publication title -
gematologiâ i transfuziologiâ
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.126
H-Index - 5
eISSN - 2411-3042
pISSN - 0234-5730
DOI - 10.35754/0234-5730-2021-66-2-206-217
Subject(s) - human leukocyte antigen , typing , allele , biology , transplantation , genetics , dna sequencing , hematopoietic stem cell transplantation , gene , immunology , stem cell , medicine , antigen
. The patient survival after allogeneic haematopoietic stem cell transplantation (allo-HSCT) from an unrelated or related haploidentical donor is improved in a donor–recipient match resolution at the level of non-coding region identity of HLA genes. Next-generation sequencing (NGS) allows detection of point substitutions in HLA non-coding regions. Aim — assessment of the NGS-based HLA-typing performance. Materials and methods . An NGS-based HLA-typing of 1,056 DNA samples from allo-HSCT recipients, their related and registry donors was performed with AllTypekit chemistry (OneLambda, USA). A parallel HLA-typing assay of 96 samples by 8 genes (A/B/C/DRB1/DRB3/DRB4/DRB5/DQB1) was accomplished within one working week. Results . HLA class I genes were typed at a 4-field (allelic), and HLA class II genes — 2–4-field (high to allelic) resolution. An allelic-resolution typing of HLA class I genes in a Russian population (657 registry donors) was conducted for the first time. The most frequent HLA alleles have been identified: А*02:01:01:01 in HLA-A (26.9 %), B*07:02:01:01 in HLA-B (12.5 %) and C*07:02:01:03 in HLA-C (12.6 %). The most frequent HLA class II variants were DRB1*07:01:01 (14.1 %), DRB3*02:01:01 (18.0 %), DRB4*01:03:01 (18.9 %), DRB5*01:01:01 (13.5 %), DQB1*03:01P (17.4 %). Conclusion . An NGS-geared HLA-typing has yielded low-ambiguity allelic and high-level resolution results in a parallel sequencing assay with a large number of samples. The method implemented detects genetic polymorphisms also in non-exonic non-coding regions of HLA genes and facilitates typing in candidate HSCT recipients, related and unrelated donors.