Whole-organism eQTL mapping at cellular resolution with single-cell sequencing
- The Hebrew University of Jerusalem, Israel
- University of California, Los Angeles, United States
Abstract
Genetic regulation of gene expression underlies variation in disease risk and other complex traits. The effect of expression quantitative trait loci (eQTLs) varies across cell types; however, the complexity of mammalian tissues makes studying cell-type eQTLs highly challenging. We developed a novel approach in the model nematode Caenorhabditis elegans that uses single cell RNA sequencing to map eQTLs at cellular resolution in a single one-pot experiment. We mapped eQTLs across cell types in an extremely large population of genetically distinct C. elegans individuals. We found cell-type-specific trans-eQTL hotspots that affect the expression of core pathways in the relevant cell types. Finally, we found single-cell-specific eQTL effects in the nervous system, including an eQTL with opposite effects in two individual neurons. Our results show that eQTL effects can be specific down to the level of single cells.
Data availability
Raw sequencing data are available under NCBI bioproject PRJNA658829.
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QX recombinant inbred advanced intercross lines of C. elegansNCBI Gene Expression Omnibus, GSE23857.
Article and author information
Author details
Funding
National Human Genome Research Institute (K99-HG010369)
- Eyal Ben-David
National Human Genome Research Institute (R01-HG004321)
- Leonid Kruglyak
Howard Hughes Medical Institute (Investigator award)
- Leonid Kruglyak
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2021, Ben-David et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Whole-organism eQTL mapping at cellular resolution with single-cell sequencing
eLife 10:e65857.
https://doi.org/10.7554/eLife.65857
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