Genetics of trans-regulatory variation in gene expression

Frank Wolfgang Albert, Joshua S. Bloom, Jake Siegel, Laura Day, Leonid Kruglyak

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

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 1012 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.

Original languageEnglish (US)
Article numbere35471
JournaleLife
Volume7
DOIs
StatePublished - Jul 17 2018

Bibliographical note

Funding Information:
We thank Noorossadat Torabi for unpublished ASE data, Meru Sadhu and Olga Schubert for comments on the manuscript, and the Minnesota Supercomputing Institute (MSI) at the University of Minnesota for computational resources. Howard Hughes Medical Institute Leonid Kruglyak National Institute of General Medical Sciences R01GM102308 Leonid Kruglyak National Institute of General Medical Sciences 1R35GM124676-01 Frank Wolfgang Albert.

Publisher Copyright:
© Albert et al.

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