PDF(Pubmed)
Abstract：
Immunoglobulins (IGs), critical components of the human immune system, are composed of heavy and light protein chains encoded at three genomic loci. The IG Kappa (IGK) chain locus consists of two large, inverted segmental duplications. The complexity of the IG loci has hindered use of standard high-throughput methods for characterizing genetic variation within these regions. To overcome these limitations, we use long-read sequencing to create haplotype-resolved IGK assemblies in an ancestrally diverse cohort (n = 36), representing the first comprehensive description of IGK haplotype variation. We identify extensive locus polymorphism, including novel single nucleotide variants (SNVs) and novel structural variants harboring functional IGKV genes. Among 47 functional IGKV genes, we identify 145 alleles, 67 of which were not previously curated. We report inter-population differences in allele frequencies for 10 IGKV genes, including alleles unique to specific populations within this dataset. We identify haplotypes carrying signatures of gene conversion that associate with SNV enrichment in the IGK distal region, and a haplotype with an inversion spanning the proximal and distal regions. These data provide a critical resource of curated genomic reference information from diverse ancestries, laying a foundation for advancing our understanding of population-level genetic variation in the IGK locus.
摘要：
免疫球蛋白(IGs),人体免疫系统的关键组成部分，由三个基因组基因座编码的重链和轻链组成。IGκ(IGK)链基因座由两个大的、反向分段重复。IG基因座的复杂性阻碍了使用标准的高通量方法来表征这些区域内的遗传变异。为了克服这些限制,我们使用长读数测序在祖先不同的队列中创建单倍型分辨的IGK组件（n=36），代表IGK单倍型变异的第一个全面描述。我们确定了广泛的基因座多态性，包括新型单核苷酸变体(SNV)和具有功能性IGKV基因的新型结构变体。在47个功能性IGKV基因中，我们鉴定出145个等位基因,其中67个以前没有策划过。我们报告了10个IGKV基因的等位基因频率的群体间差异，包括该数据集中特定群体特有的等位基因。我们鉴定了携带与IGK远端区域SNV富集相关的基因转换特征的单倍型。和跨越近端和远端区域的倒置的单倍型。这些数据提供了来自不同祖先的精选基因组参考信息的关键资源，为推进我们对IGK位点群体水平遗传变异的理解奠定了基础。
