Abstract：
HLA genes play a major role for successful hematopoietic stem cell transplantation (HSCT). While the success of HSCT depends on a HLA compatibility between donor and patient, finding a suitable donor remains challenging because of the high polymorphic nature of HLA genes. In this study, HLA-A, -B, -C, -DRB1 and -DQB1 alleles were genotyped at the 3-fields resolution level using MiSeq Illumina of 3341 Russian volunteers from the Kirov bone marrow Registry. Full gene of HLA-A, -B and -C, exons 2-4 of HLA-DRB1 and exons 1-5 of HLA-DQB1 were amplified by multiplex long-range polymerase chain reaction (PCR) and each allele was determined by matching the targeted regions and the reference sequence consisting of the IPD-IMGT/HLA Database. A total of 79 alleles of HLA-A, 115 alleles of HLA-B, 67 alleles of HLA-C, 71 alleles of HLA-DRB1 and 34 alleles of HLA-DQB1 were identified. According to common, intermediate and well-documented catalogs, 38 alleles in HLA-A, 69 in HLA-B, 39 in HLA-C, 48 in HLA-DRB1 and 21 in HLA-DQB1 locus were common alleles, and 5, 7, 7, 7, 2 kinds, accordingly, to written above were well-documented alleles. A total of 12 novel alleles including 3 alleles in HLA-A, 3 alleles in HLA-B, 1 allele in HLA-C, 2 alleles in HLA-DRB1 and 3 alleles in HLA-DQB1 loci were found. Six haplotypes with a frequency of more than 1.0% accounted for 13.19% of the total haplotype frequencies. This information on rare and novel alleles found by HLA typing with NGS may be helpful for unrelated HSCT among Russians.
摘要：
HLA基因在成功的造血干细胞移植(HSCT)中起主要作用。虽然HSCT的成功取决于供体和患者之间的HLA相容性，由于HLA基因的高度多态性质，寻找合适的供体仍然具有挑战性。在这项研究中,HLA-A,-B,-C,使用来自Kirov骨髓登记处的3,341名俄罗斯志愿者的MiSeqIllumina，以3场分辨率水平对-DRB1和-DQB1等位基因进行了基因分型。HLA-A全基因,-B和-C,通过多重长程聚合酶链反应(PCR)扩增HLA-DRB1的外显子2-4和HLA-DQB1的外显子1-5,并通过匹配目标区域和由IPD-IMGT/HLA数据库组成的参考序列确定每个等位基因.HLA-A的79个等位基因,HLA-B的115个等位基因，HLA-C的67个等位基因，鉴定了HLA-DRB1的71个等位基因和HLA-DQB1的34个等位基因。根据普通,中间和有据可查的目录，HLA-A中的38个等位基因，69在HLA-B中，39在HLA-C中，HLA-DRB1中的48个和HLA-DQB1基因座中的21个是常见等位基因，和5，7，7，7，2种，因此,上面写的是有据可查的等位基因。12个新等位基因，包括HLA-A中的3个等位基因，HLA-B中的3个等位基因，HLA-C中的1个等位基因,发现HLA-DRB1中的2个等位基因和HLA-DQB1基因座中的3个等位基因。频率超过1.0％的六个单倍型占总单倍型频率的13.19％。通过使用NGS进行HLA分型发现的有关稀有和新等位基因的信息可能对俄罗斯人中无关的HSCT有所帮助。本文受版权保护。保留所有权利。
