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.

表型变异是涉及染色体增减的疾病（如唐氏综合征和癌症）的显著特征。等位基因变异曾被认为是这种异质性的唯一原因。本研究系统分析了单条或多条染色体增减的后果，结果表明非整倍体状态（aneuploid state）可引发非遗传性表型变异。携带相同明确非整倍体（aneuploidy）的酵母细胞群体，在细胞周期进程和环境扰动响应方面表现出异质性。变异程度随非整倍体程度增加而上升，部分源于基因拷贝数失衡；这表明基因表达的细微变化会影响生物网络的稳健性，当此类变化发生在多个基因时，会导致不同的行为表现。由于近交三体小鼠也表现出可变表型，我们进一步提出，非遗传性个体差异是非整倍体状态的普遍特征，这可能导致非整倍体引发疾病的表现型和治疗反应存在差异。