1. Chromosomes and Gene Expression
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Genetics of trans-regulatory variation in gene expression

  1. Frank Wolfgang Albert  Is a corresponding author
  2. Joshua S Bloom  Is a corresponding author
  3. Jake Siegel
  4. Laura Day
  5. Leonid Kruglyak  Is a corresponding author
  1. University of Minnesota, United States
  2. University of California, Los Angeles, United States
Research Article
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Cite this article as: eLife 2018;7:e35471 doi: 10.7554/eLife.35471

Abstract

Heritable variation in gene expression forms a crucial bridge between genomic variation and the biology of many traits. However, most expression quantitative trait loci (eQTLs) remain unidentified. We mapped eQTLs by transcriptome sequencing in 1,012 yeast segregants. The resulting eQTLs accounted for over 70% of the heritability of mRNA levels, allowing comprehensive dissection of regulatory variation. Most genes had multiple eQTLs. Most expression variation arose from trans-acting eQTLs distant from their target genes. Nearly all trans-eQTLs clustered at 102 hotspot locations, some of which influenced the expression of thousands of genes. Fine-mapped hotspot regions were enriched for transcription factor genes. While most genes had a local eQTL, most of these had no detectable effects on the expression of other genes in trans. Hundreds of non-additive genetic interactions accounted for small fractions of expression variation. These results reveal the complexity of genetic influences on transcriptome variation in unprecedented depth and detail.

Data availability

Sequencing reads have been deposited at SRA under accession codes SRP148919 and SRP149494. Processed datasets are included with this manuscript, and are also available in a FigShare repository at https://figshare.com/s/83bddc1ddf3f97108ad4. All data are available freely and without restriction.

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

Article and author information

Author details

  1. Frank Wolfgang Albert

    Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, United States
    For correspondence
    falbert@umn.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1380-8063
  2. Joshua S Bloom

    Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    jbloom@mednet.ucla.edu
    Competing interests
    No competing interests declared.
  3. Jake Siegel

    Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  4. Laura Day

    Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    No competing interests declared.
  5. Leonid Kruglyak

    Department of Human Genetics, University of California, Los Angeles, Los Angeles, United States
    For correspondence
    LKruglyak@mednet.ucla.edu
    Competing interests
    Leonid Kruglyak, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8065-3057

Funding

Howard Hughes Medical Institute (Investigator)

  • Leonid Kruglyak

National Institute of General Medical Sciences (R01GM102308)

  • Leonid Kruglyak

National Institute of General Medical Sciences (1R35GM124676-01)

  • Frank Wolfgang Albert

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Patricia J Wittkopp, University of Michigan, United States

Publication history

  1. Received: January 28, 2018
  2. Accepted: June 30, 2018
  3. Accepted Manuscript published: July 17, 2018 (version 1)
  4. Version of Record published: August 2, 2018 (version 2)

Copyright

© 2018, Albert 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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