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Science. 2019 Jun 28;364(6447):1287-1290. doi: 10.1126/science.aaw0040.

Dynamic genetic regulation of gene expression during cellular differentiation.

Author information

1
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
2
Committee on Genetics, Genomics, and Systems Biology, University of Chicago, Chicago, IL 60637, USA.
3
Interdisciplinary Scientist Training Program, University of Chicago, Chicago, IL 60637, USA.
4
Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
5
Department of Computer Science, Johns Hopkins University, Baltimore, MD 21218, USA.
6
Department of Applied Mathematics and Statistics, Johns Hopkins University, Baltimore, MD 21218, USA.
7
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA. ajbattle@jhu.edu gilad@uchicago.edu.
8
Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA. ajbattle@jhu.edu gilad@uchicago.edu.
9
Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
#
Contributed equally

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.

PMID:
31249060
PMCID:
PMC6623972
[Available on 2019-12-28]
DOI:
10.1126/science.aaw0040

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