Laboratory for Human Immunogenetics, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan.
Genes (Basel). 2023 Feb 24;14(3):572. doi: 10.3390/genes14030572.
Common variants strongly influence the risk of human autoimmunity. Two categories of variants contribute substantially to the risk: (i) coding variants of genes and (ii) non-coding variants at the non- loci. We recently developed a novel analytic pipeline of T cell receptor (TCR) repertoire to understand how coding variants influence the risk. We identified that the risk variants increase the frequency of auto-reactive T cells. In addition, to understand how non-coding variants contribute to the risk, the researchers conducted integrative analyses using expression quantitative trait loci (eQTL) and splicing quantitative trait loci (sQTL) and demonstrated that the risk non-coding variants dysregulate specific genes' expression and splicing. These studies provided novel insight into the immunological consequences of two major genetic risks, and we will introduce these research achievements in detail in this review.
常见变异强烈影响人类自身免疫的风险。两类变异对风险有重要贡献：(i) 基因的编码变异和 (ii) 非 基因座的非编码变异。我们最近开发了一种新的 T 细胞受体 (TCR) 库分析管道，以了解 编码变异如何影响风险。我们发现风险变异增加了自身反应性 T 细胞的频率。此外，为了了解非编码变异如何导致风险，研究人员使用表达数量性状基因座 (eQTL) 和剪接数量性状基因座 (sQTL) 进行综合分析，并表明风险非编码变异会扰乱特定基因的表达和剪接。这些研究为两种主要遗传风险的免疫学后果提供了新的见解，我们将在这篇综述中详细介绍这些研究成果。
