瑞典卡罗林斯卡学院Gunilla B. Karlsson Hedestam小组的论文发现了对全球25个人群的超高通量IGH基因分型揭示了群体偏倚的等位基因多样性和纯合的V和D基因缺失。相关论文于2026年3月16日发表在《免疫学》杂志上。

该团队介绍了ImmuneDiscover，这是一个超高通量测序平台，可以从纳克级别的DNA中进行个体化IG基因分型，并同时分析超过1000个个体。利用ImmuneDiscover，该团队为来自1000个基因组计划的2486个个体生成了高分辨率的IG基因型，跨越了不同的种群祖先，并建立了Karolinska研究所适应性免疫受体基因变异图谱（KIARVA），这是一个开放获取的IG基因变异图谱。

与来自100多万个基因组的单核苷酸多态性数据进行交叉验证，证实了所发现等位基因的准确性。他们的分析揭示了群体特异性模式，包括在多达30%的东亚个体中发现的多基因IG重链多样性（IGHD）缺失，以及与疾病相关位点相关的单倍型差异。这些发现阐明了形成IG基因多样性的进化力量，并为研究全球病原体敏感性和疫苗反应性的免疫遗传学基础提供了基础。

研究人员表示，人类免疫球蛋白（IG）基因的非凡多样性支撑着有效的抗体反应，然而，种系编码的IG变异在人群中的全部范围和功能影响在很大程度上是未知的。

附：英文原文

Title: Ultra-high-throughput IGH genotyping of 25 global populations reveals population-biased allelic diversity and homozygous V and D gene deletions

Author: Martin Corcoran, Sanjana Narang, Mateusz Kaduk, Mark Chernyshev, Anna Frnert, Christopher Sundling, Gunilla B. Karlsson Hedestam

Issue&Volume: 2026-03-16

Abstract: The extraordinary diversity of human immunoglobulin (IG) genes underpins effective antibody responses, yet the full scope and functional impact of germline-encoded IG variation across populations is largely unknown. Here, we present ImmuneDiscover, an ultra-high-throughput sequencing platform enabling individualized IG genotyping from nanogram-scale DNA and simultaneous analysis of over 1,000 individuals. Using ImmuneDiscover, we generated high-resolution IG genotypes for 2,486 individuals from the 1,000 Genomes Project, spanning diverse population ancestries, and built Karolinska Institutet Adaptive Immune Receptor Gene Variant Atlas (KIARVA), an open access atlas of IG gene variation. Cross-validation with single-nucleotide polymorphism data from over one million genomes confirmed the accuracy of discovered alleles. Our analysis reveals population-specific patterns, including a multigene IG heavy-chain diversity (IGHD) deletion found homozygously in up to 30% of East Asian individuals, and haplotypic differences linked to disease-associated loci. These findings illuminate the evolutionary forces shaping IG gene diversity and provide a foundational resource for investigating the immunogenetic basis of pathogen susceptibility and vaccine responsiveness worldwide.

DOI: 10.1016/j.immuni.2026.01.026

Source: https://www.cell.com/immunity/abstract/S1074-7613(26)00047-6