Whole-organism eQTL mapping at cellular resolution with single-cell sequencing

Abstract
Data availability
Article and author information
Metrics

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.

The following data sets were generated

1. Ben-David E
2. Boocock J
3. Guo L
4. Zdraljevic S
5. Bloom JS
6. Kruglyak L
(2020) Whole-organism mapping of the genetics of gene expression at cellular resolution
NCBI, SRP279842.

https://trace.ncbi.nlm.nih.gov/Traces/sra/?study=SRP279842

The following previously published data sets were used

(2012) QX recombinant inbred advanced intercross lines of C. elegans
NCBI Gene Expression Omnibus, GSE23857.

https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE23857

Article and author information

Author details

Eyal Ben-David

Biochemistry and Molecular Biology, The Hebrew University of Jerusalem, Jerusalem, Israel

For correspondence
eyal.bendavid@mail.huji.ac.il

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-0514-0400
James Boocock

Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Longhua Guo

Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Stefan Zdraljevic

Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States

Competing interests
The authors declare that no competing interests exist.
Joshua S Bloom

Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States

For correspondence
jbloom@mednet.ucla.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7241-1648
Leonid Kruglyak

Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States

For correspondence
LKruglyak@mednet.ucla.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-8065-3057

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

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.