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ENGLISH ABSTRACT
新等位基因 HLA-DRB1*12：106 1例的确认
董丽娜
陈男英
何亿镇
章伟
朱发明
作者及单位信息
·
DOI： 10.3760/cma.j.cn511374-20240627-00355
Identification of a case with novel HLA-DRB1*12: 106 allele
Dong Li′na
Chen Nanying
He Yizhen
Zhang Wei
Zhu Faming
Authors Info & Affiliations
Dong Li′na
Blood Center of Zhejiang Province, Hangzhou, Zhejiang 310052, China
Chen Nanying
Blood Center of Zhejiang Province, Hangzhou, Zhejiang 310052, China
He Yizhen
Blood Center of Zhejiang Province, Hangzhou, Zhejiang 310052, China
Zhang Wei
Blood Center of Zhejiang Province, Hangzhou, Zhejiang 310052, China
Zhu Faming
Blood Center of Zhejiang Province, Hangzhou, Zhejiang 310052, China
·
DOI： 10.3760/cma.j.cn511374-20240627-00355
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摘要

目的鉴定 HLA新等位基因 HLA-DRB1*12：106的核苷酸序列。

方法以1名浙江省血液中心2023年入库检测的血小板献血者为研究对象，用基于AllType NGS 11位点、AllType FASTplex NGS试剂的二代测序以及Sanger测序方法对其进行 HLA基因分型。用uTYPE 7.3和TypeStream Visual 3.0软件分别判定两种测序方法提示的献血者 HLA基因型。本研究通过了浙江省血液中心伦理委员会的审查(批准号：省血液中心伦审2022年研第001号)。

结果发现献血者携带1个 HLA-DRB1*12新等位基因，将其全部编码序列(801 bp)提交GenBank数据库(编号为OR101190)。该序列被世界卫生组织 HLA系统因子命名委员会正式命名为 HLA-DRB1*12：106(提交编号为HWS10066755)。与其同源性最高的 HLA-DRB1*12：01：01：01等位基因序列相比， HLA-DRB1*12：106第2外显子第344位的碱基T变异为G，导致第86位的缬氨酸替换为甘氨酸。献血者的 HLA基因型被确定为 HLA-A*02：01，11：01；-B*13：02，40：01；-C*01：02，03：03；-DRB1*07：01，12：106；-DRB3*01：01；-DRB4*01：03；-DQA1*02：01，04：01；-DQB1*02：02，04：02；-DPA1*01：03，01：03；-DPB1*02：01：02G，04：01：01G。

结论在中国人群中确认了1个新的 HLA-DRB1等位基因，其变异氨基酸位于β链的肽结合区，可能影响潜在抗原肽的结合特性。

HLA-DRB1基因 ;二代测序;Sanger测序
ABSTRACT

ObjectiveTo identify the nucleotide sequence of a novel HLA-DRB1*12: 106 allele.

MethodsA blood donor who was joined into the database for platelet matching transfusion at the Blood Center of Zhejiang Province in 2023 was selected as the study subject. HLA genotyping was carried out through next-generation sequencing based on AllType NGS 11 locus, AllType FASTPlex NGS reagents, and Sanger sequencing method. The HLA genotype of the donor by Sanger sequencing and next generation sequencing were assigned by using uTYPE 7.3 and TypeStream Visual 3.0 software, respectively. This study was approved by Medical Ethics Committee of the Zhejiang Blood Center (Ethics No. Provincial Blood Center Ethics Review 2022 Research No. 001).

ResultsA novel HLA-DRB1*12 allele has been identified, and the full coding sequence has been submitted to the GenBank database (No. OR101190), and the length of submitted sequence was 801 bp, which was officially named as HLA-DRB1*12: 106 by the WHO Nomenclature Committee for Factors of the HLA System (submission No. HWS10066755). Compared with the sequence of the highest homology ( HLA-DRB1*12: 01: 01: 01 allele), a single nucleotide change was identified at position 344 T>G in the exon 2 of the HLA-DRB1*12: 106, which has resulted in replacement of Valine by Glycine at residue 86. The HLA genotype of the proband was determined as HLA-A*02: 01, 11: 01; -B*13: 02, 40: 01; -C*01: 02, 03: 03; -DRB1*07: 01, 12: 106; -DRB3*01: 01; -DRB4*01: 03; -DQA1*02: 01, 04: 01; -DQB1*02: 02, 04: 02; -DPA1*01: 03, 01: 03; -DPB1*02: 01: 02G, 04: 01: 01G.

ConclusionA novel HLA-DRB1 allele has been identified in the Chinese population. The mutated amino acid, located in the peptide binding region of the β chain, may affect the binding characteristics of antigen peptides.

HLA-DRB1 gene ;Next generation sequencing;Sanger sequencing
Zhu Faming, Email: mocdef.labiamtoh00mfz
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引用本文

董丽娜,陈男英,何亿镇,等. 新等位基因 HLA-DRB1*12：106 1例的确认 [J]. 中华医学遗传学杂志,2025,42(02)：151-155.

DOI:10.3760/cma.j.cn511374-20240627-00355

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人类白细胞抗原(human leucocyte antigen， HLA)基因分型被广泛用于造血干细胞捐献者资料库建立、供受者 HLA配合选择、血小板配合性输注的献血者资料库建立以及疾病诊断等 [ 1 , 2 , 3 ]。 HLA-DRB1属于经典的 HLA-Ⅱ类基因，也是 HLA-Ⅱ类区域多态性最丰富的基因，编码HLA-DR抗原的β链，对造血干细胞/器官移植、病毒感染、糖尿病易感性等方面具有重要的参考价值 [ 4 , 5 , 6 , 7 ]。 HLA-DRB1*11等位基因可作为输血依赖性地中海贫血患者同种抗体产生的预测因子 [ 8 ]， HLA-DRB1*12等位基因可能对乙肝病毒感染具有保护作用 [ 9 ]，而某些 HLA-DRB1等位基因则与1型糖尿病的易感性显著相关 [ 10 ]。 HLA-DRB1基因全长约13 kb，共包含6个外显子，编码序列长度为801 bp，其中第1外显子编码前导肽，第2、3外显子编码DR抗原β链的β1和β2胞外结构域，第4外显子编码跨膜区结构域，第5、6外显子编码细胞质尾部 [ 11 ]。HLA-DR抗原特异性主要由 HLA-DRB1基因的第2外显子决定，后者编码多肽结合区，又称抗原识别功能区(antigen recognition domain，ARD)。随着测序技术的发展，已发现的 HLA-DRB1等位基因不断增加 [ 12 ]。本研究发现了1个变异在第2外显子的 HLA-DRB1新等位基因，并用不同的测序方法对其进行了确认，具体报告如下。
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备注信息
A
朱发明，Email： mocdef.labiamtoh00mfz
B

董丽娜：实施研究、分析/解释数据、起草文章、获取研究经费；陈男英：实施研究、分析/解释数据；何亿镇：实施研究、采集数据、统计分析；章伟：酝酿和设计实验、分析/解释数据、行政/技术/材料支持；朱发明：酝酿和设计实验、起草文章、批评性审阅、指导

C
所有作者均声明不存在利益冲突
D
浙江省医药卫生科技计划项目 (2022KY733、2024KY939)
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