Variability in gene expression across a population of homogeneous cells is known to influence various biological processes. In model organisms, natural genetic variants were found that modify expression dispersion (variability at a fixed mean) but very few studies have detected such effects in humans. Here, we analyzed single-cell expression of four proteins (CD23, CD55, CD63 and CD86) across cell lines derived from individuals of the Yoruba population. Using data from over 30 million cells, we found substantial inter-individual variation of dispersion. We demonstrate, via de novo cell line generation and subcloning experiments, that this variation exceeds the variation associated with cellular immortalization. We detected a genetic association between the expression dispersion of CD63 and the rs971 SNP. Our results show that human DNA variants can have inherently-probabilistic effects on gene expression. Such subtle genetic effects may participate to phenotypic variation and disease outcome.

已知在整个同质细胞群体中基因表达的差异会影响各种生物学过程。在模型生物中，发现了天然的遗传变异可以改变表达的分散性（固定平均值的变异性），但是很少有研究在人类中发现这种作用。在这里，我们分析了来自约鲁巴族个体的细胞系中四种蛋白质（CD23，CD55，CD63和CD86）的单细胞表达。使用来自超过3千万个细胞的数据，我们发现个体之间的色散存在很大差异。我们通过从头细胞系生成和亚克隆实验证明，这种变异超出了与细胞永生化相关的变异。我们检测到CD63的表达分散与rs971之间存在遗传关联SNP。我们的结果表明，人类DNA变体可以对基因表达产生内在的概率影响。这种微妙的遗传效应可能参与表型变异和疾病结果。