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Dynamic genetic regulation of gene expression during cellular differentiation

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Science  28 Jun 2019:
Vol. 364, Issue 6447, pp. 1287-1290
DOI: 10.1126/science.aaw0040

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Variants affect gene expression over time

Genetic variation drives the spectrum of human phenotypes but in some cases has been linked to pathological conditions. Strober et al. set out to explore how genetic diversity regulates gene expression in cell differentiation over time. They examined expression quantitative trait loci (eQTLS)—genetic variants correlated with gene expression—in induced pluripotent stem cell lines from 19 Yoruban individuals at 16 time points during differentiation into cardiomyocytes. They identified hundreds of developmental stage–specific eQTLs. Thus, the impact of genetic variations depends on the developmental context or tissue under observation.

Science, this issue p. 1287

Abstract

Genetic regulation of gene expression is dynamic, as transcription can change during cell differentiation and across cell types. We mapped expression quantitative trait loci (eQTLs) throughout differentiation to elucidate the dynamics of genetic effects on cell type–specific gene expression. We generated time-series RNA sequencing data, capturing 16 time points during the differentiation of induced pluripotent stem cells to cardiomyocytes, in 19 human cell lines. We identified hundreds of dynamic eQTLs that change over time, with enrichment in enhancers of relevant cell types. We also found nonlinear dynamic eQTLs, which affect only intermediate stages of differentiation and cannot be found by using data from mature tissues. These fleeting genetic associations with gene regulation may explain some of the components of complex traits and disease. We highlight one example of a nonlinear eQTL that is associated with body mass index.

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