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

  1. Eyal Ben-David  Is a corresponding author
  2. James Boocock
  3. Longhua Guo
  4. Stefan Zdraljevic
  5. Joshua S Bloom  Is a corresponding author
  6. Leonid Kruglyak  Is a corresponding author
  1. The Hebrew University of Jerusalem, Israel
  2. 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.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0514-0400
  2. 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.
  3. 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.
  4. 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.
  5. 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.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7241-1648
  6. 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.
    ORCID icon "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.

Reviewing Editor

  1. Daniel J Kliebenstein, University of California, Davis, United States

Publication history

  1. Received: December 16, 2020
  2. Accepted: March 17, 2021
  3. Accepted Manuscript published: March 18, 2021 (version 1)
  4. Version of Record published: April 22, 2021 (version 2)

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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  1. Eyal Ben-David
  2. James Boocock
  3. Longhua Guo
  4. Stefan Zdraljevic
  5. Joshua S Bloom
  6. Leonid Kruglyak
(2021)
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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