使用下一代测序（NGS）平台研究人类白细胞抗原（HLA）等位基因和单倍型频率：印度一项针对500多名个体的单中心研究！

Study of human leukocyte antigen (HLA) allele and haplotype frequency using next generation sequencing (NGS) platform: Single-centre study of over 500 individuals in India!

作者信息

Simmi Mehra, Tiwari Aseem K, Rajni Chauhan, Gunjan Bhardwaj, Neha Rani, Shubham Kashyap, Simran Kahlon

机构信息

Molecular and Transplant Immunology Laboratory, Blood Centre, Medanta-Gurugram, Gurugram, Haryana, India.

出版信息

Transpl Immunol. 2025 Mar;89:102180. doi: 10.1016/j.trim.2025.102180. Epub 2025 Jan 30.

DOI:10.1016/j.trim.2025.102180

PMID:39892763

Abstract

BACKGROUND

The huge diversity of Human Leukocyte Antigen (HLA) system is well-known to be associated with various diseases, anthropology, population genetics, and transplantation. The frequencies of HLA alleles in different populations are crucial for both research and clinical applications. This study determined the allelic and haplotype frequencies of all HLA class I and class II loci in 595 consecutive samples from patients who underwent solid organ transplantation (SOT) and hematopoietic progenitor cell transplantation (HPCT).

METHOD

High-resolution HLA typing for HLA-A, B, C, DRB1, and DQB1 was conducted using a next generation sequencing (NGS) platform.

RESULTS

The most frequent alleles observed among all HLAs were A11:01:01 (0.1849), A24:02:01 (0.1202) and A01:01:01 (0.1143) in A locus, B40:06:01 (0.1050), B52:01:01 (0.0950) and B51:01:01 (0.0723) in B locus, C07:02:01 (0.1303), C04:01:01 (0.1227) and C15:02:01 (0.1185) in C locus, DRB107:01:01 (0.1286), DRB115:01:01 (0.1134) and DRB103:01:01 (0.0966) in DRB1 locus, and DQB106:01:01 (0.1849), DQB103:01:01 (0.1471) and DQB102:02:01 (0.0966) in DQB1 locus. The most frequent (>2 %) five-locus A ∼ B ∼ C ∼ DRB1 ∼ DQB1 haplotypes were A33:03:01 ∼ B44:03:02 ∼ C07:06:01 ∼ DQB102:02:01 ∼ DRB107:01:01 (2.97 %), A26:01:01 ∼ B08:01:01 ∼ C07:02:01 ∼ DQB102:01:01 ∼ DRB103:01:01 (2.23 %) and A02:11:01 ∼ B40:06:01 ∼ C15:02:01 ∼ DQB106:01:01 ∼ DRB115:01:01(2.15 %). Among all tested loci, the HLA-B locus had the most polymorphism, whereas the HLA-DQB1 locus had the least polymorphism.

CONCLUSION

The data represent the distribution of HLA-A, B, C, DRB1, DQB1 alleles and their haplotype frequencies among the population in India.

摘要

背景

人类白细胞抗原（HLA）系统的巨大多样性与多种疾病、人类学、群体遗传学及移植相关，这是广为人知的。不同人群中HLA等位基因的频率对于研究和临床应用都至关重要。本研究确定了595例接受实体器官移植（SOT）和造血祖细胞移植（HPCT）患者连续样本中所有HLAⅠ类和Ⅱ类基因座的等位基因及单倍型频率。

方法

使用下一代测序（NGS）平台对HLA-A、B、C、DRB1和DQB1进行高分辨率HLA分型。

结果

在所有HLA中观察到的最常见等位基因，A基因座为A11:01:01（0.1849）、A24:02:01（0.1202）和A01:01:01（0.1143）；B基因座为B40:06:01（0.1050）、B52:01:01（0.0950）和B51:01:01（0.0723）；C基因座为C07:02:01（0.1303）、C04:01:01（0.1227）和C15:02:01（0.1185）；DRB1基因座为DRB107:01:01（0.1286）、DRB115:01:01（0.1134）和DRB103:01:01（0.0966）；DQB1基因座为DQB106:01:01（0.1849）、DQB103:01:01（0.1471）和DQB102:02:01（0.0966）。最常见的（>2%）五位点A∼B∼C∼DRB1∼DQB1单倍型为A33:03:01∼B44:03:02∼C07:06:01∼DQB102:02:01∼DRB107:01:01（2.97%）、A26:01:01∼B08:01:01∼C07:02:01∼DQB102:01:01∼DRB103:01:01（2.23%）和A02:11:01∼B40:06:01∼C15:02:01∼DQB106:01:01∼DRB115:01:01（2.15%）。在所有检测的基因座中，HLA-B基因座多态性最高，而HLA-DQB1基因座多态性最低。