Cell-to-cell expression dispersion of B-cell surface proteins displays genetic variation among humans
Domaine:
healthcareCréateur:
GérClaOrsSté
Éditeur:
ope
Hôte:
ABSTRACT
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 whether such effects exist in humans has not been fully demonstrated. 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. By association mapping, we linked the expression dispersion of CD63 to 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 predisposition.
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