Genetics of trans -regulatory variation in gene expression

ELife
Frank W AlbertLeonid Kruglyak

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.

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Citations

May 28, 2019·Molecular & Cellular Proteomics : MCP·Burcu VitrinelChristine Vogel
Apr 23, 2020·Molecular Biology and Evolution·Emily B JosephsJohn R Stinchcombe
May 3, 2020·Molecular Biology and Evolution·Christian BrionJoseph Schacherer
May 10, 2020·G3 : Genes - Genomes - Genetics·Kathryn S Evans, Erik C Andersen
Jul 24, 2020·Genome Research·Gat KriegerNaama Barkai
Jun 20, 2020·ELife·Marie PereiraJacques Behmoaras
Oct 2, 2019·Proceedings of the National Academy of Sciences of the United States of America·Andrea Hodgins-DavisPatricia J Wittkopp
Nov 27, 2020·Frontiers in Genetics·Mark G SterkenBasten L Snoek
Aug 5, 2019·Trends in Plant Science·Nathan SpringerErich Grotewold
Aug 9, 2019·Molecular & Cellular Proteomics : MCP·Burcu VitrinelChristine Vogel
Nov 20, 2020·BMC Genomics·Ju Hun ChoiJong Wha J Joo
Dec 4, 2020·Nature Reviews. Genetics·Mark S HillPatricia J Wittkopp
Apr 1, 2021·Genetics·Krisna Van DykeFrank W Albert
May 8, 2021·Genome Biology·Saikat BanerjeeJohannes Söding
May 28, 2021·Molecular Systems Biology·Leopold PartsJolanda van Leeuwen
Oct 1, 2021·BMC Ecology and Evolution·Alexander F KernHunter B Fraser

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Datasets Mentioned

BETA
SRP149494

Methods Mentioned

BETA
RNA-seq
PCR
genotyping
SMA

Software Mentioned

R car
R igraph
Kallisto
R package grofit
R package caret
SGD
rrBLUP
R
BioMek
rrBLUP R package

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