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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.

Cell-to-cell expression dispersion of B-cell surface proteins is linked to genetic variants in humans