Data from: Aneuploidy causes non-genetic individuality

Phenotypic variability is a hallmark of diseases involving chromosome gains and losses, such as Down syndrome and cancer. Allelic variances have been thought to be the sole cause of this heterogeneity. Here, we systematically examine the consequences of gaining and losing single or multiple chromosomes to show that the aneuploid state causes non-genetic phenotypic variability. Yeast cell populations harboring the same defined aneuploidy exhibit heterogeneity in cell-cycle progression and response to environmental perturbations. Variability increases with degree of aneuploidy and is partly due to gene copy number imbalances, suggesting that subtle changes in gene expression impact the robustness of biological networks and cause alternate behaviors when they occur across many genes. As inbred trisomic mice also exhibit variable phenotypes, we further propose that non-genetic individuality is a universal characteristic of the aneuploid state that may contribute to variability in presentation and treatment responses of diseases caused by aneuploidy.

表型变异 (phenotypic variability) 是染色体数目增减相关疾病（如唐氏综合征 (Down syndrome) 与癌症）的标志性特征。长期以来，学界普遍认为等位基因变异 (allelic variances) 是这类异质性的唯一诱因。本研究通过系统探究单条或多条染色体数目增减所产生的影响，证实非整倍体 (aneuploid) 状态可引发非遗传性表型变异。携带同一明确非整倍体的酵母细胞群体，在细胞周期进程与环境扰动响应层面均表现出异质性。该变异程度随非整倍体程度升高而加剧，且部分源于基因拷贝数失衡，这提示基因表达的细微变化会影响生物网络的鲁棒性，当这类变化波及多个基因时，便会引发细胞行为的异质性。鉴于近交三体小鼠同样表现出可变表型，我们进一步提出：非遗传个体性是非整倍体状态的普遍特征，这或许会在非整倍体引发的疾病的临床表现与治疗响应差异中起到推动作用。