The Jackson Laboratory, Bar Harbor, ME, USA.
The Jackson Laboratory, Bar Harbor, ME, USA; Tufts Graduate School of Biomedical Sciences, Boston, MA, USA.
Trends Genet. 2021 Mar;37(3):251-265. doi: 10.1016/j.tig.2020.09.007. Epub 2020 Sep 30.
Interrogation of disease-relevant cellular and molecular traits exhibited by genetically diverse cell populations enables in vitro systems genetics approaches for uncovering the basic properties of cellular function and identity. Primary cells, stem cells, and organoids derived from genetically diverse mouse strains, such as Collaborative Cross and Diversity Outbred populations, offer the opportunity for parallel in vitro/in vivo screening. These panels provide genetic resolution for variant discovery and functional characterization, as well as disease modeling and in vivo validation capabilities. Here we review mouse cellular systems genetics approaches for characterizing the influence of genetic variation on signaling networks and phenotypic diversity, and we discuss approaches for data integration and cross-species validation.
对具有遗传多样性的细胞群体表现出的与疾病相关的细胞和分子特征进行研究,使体外系统遗传学方法能够揭示细胞功能和特性的基本性质。从遗传多样性的小鼠品系(如合作交叉和多样化杂交群体)中衍生出的原代细胞、干细胞和类器官,为体外/体内平行筛选提供了机会。这些面板为变体发现和功能特征分析、疾病建模和体内验证能力提供了遗传分辨率。在这里,我们回顾了用于描述遗传变异对信号网络和表型多样性影响的小鼠细胞系统遗传学方法,并讨论了数据整合和跨物种验证的方法。