Systems Genetics Group, Oak Ridge National Laboratory, Oak Ridge;
Physiol Genomics. 2010 May;41(3):244-53. doi: 10.1152/physiolgenomics.00020.2010. Epub 2010 Feb 23.
The immune system plays a pivotal role in the susceptibility to and progression of a variety of diseases. Due to a strong genetic basis, heritable differences in immune function may contribute to differential disease susceptibility between individuals. Genetic reference populations, such as the BXD (C57BL/6J × DBA/2J) panel of recombinant inbred (RI) mouse strains, provide unique models through which to integrate baseline phenotypes in healthy individuals with heritable risk for disease because of the ability to combine data collected from these populations across both multiple studies and time. We performed basic immunophenotyping (e.g., percentage of circulating B and T lymphocytes and CD4(+) and CD8(+) T cell subpopulations) in peripheral blood of healthy mice from 41 BXD RI strains to define the immunophenotypic variation in this strain panel and to characterize the genetic architecture that underlies these traits. Significant QTL models that explained the majority (50-77%) of phenotypic variance were derived for each trait and for the T:B cell and CD4(+):CD8(+) ratios. Combining QTL mapping with spleen gene expression data uncovered two quantitative trait transcripts, Ptprk and Acp1, as candidates for heritable differences in the relative abundance of helper and cytotoxic T cells. These data will be valuable in extracting genetic correlates of the immune system in the BXD panel. In addition, they will be a useful resource for prospective, phenotype-driven model selection to test hypotheses about differential disease or environmental susceptibility between individuals with baseline differences in the composition of the immune system.
免疫系统在多种疾病的易感性和进展中起着关键作用。由于遗传基础较强，免疫功能的遗传性差异可能导致个体之间对疾病的易感性存在差异。遗传参考群体，如 BXD（C57BL/6J × DBA/2J）重组近交系（RI）小鼠品系图谱，提供了独特的模型，可以将健康个体的基础表型与疾病遗传风险整合在一起，因为能够将来自这些群体的数据结合起来跨越多个研究和时间进行收集。我们对 41 个 BXD RI 品系的健康小鼠外周血进行了基本免疫表型分析（例如，循环 B 和 T 淋巴细胞以及 CD4(+)和 CD8(+)T 细胞亚群的百分比），以确定该品系图谱中的免疫表型变异性，并描述这些特征的遗传结构。为每个特征以及 T:B 细胞和 CD4(+):CD8(+) 比值导出了能够解释大部分（50-77%）表型方差的显著 QTL 模型。将 QTL 作图与脾基因表达数据相结合，揭示了两个数量性状转录本 Ptprk 和 Acp1，它们是辅助性和细胞毒性 T 细胞相对丰度遗传性差异的候选基因。这些数据将在 BXD 图谱中提取免疫系统的遗传相关性方面具有重要价值。此外，它们将是一个有价值的资源，可用于前瞻性、表型驱动的模型选择，以测试关于具有免疫系统组成差异的个体在疾病或环境易感性方面存在差异的假设。
