Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast

Abstract Unraveling the genetic sources of gene expression variation is essential to better understand the origins of phenotypic diversity in natural populations. Genome-wide association studies identified thousands of variants involved in gene expression variation, however, variants detected only e...

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Main Authors: Andreas Tsouris, Gauthier Brach, Anne Friedrich, Jing Hou, Joseph Schacherer
Format: Article
Language:English
Published: Springer Nature 2024-02-01
Series:Molecular Systems Biology
Subjects:
Online Access:https://doi.org/10.1038/s44320-024-00021-0
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author Andreas Tsouris
Gauthier Brach
Anne Friedrich
Jing Hou
Joseph Schacherer
author_facet Andreas Tsouris
Gauthier Brach
Anne Friedrich
Jing Hou
Joseph Schacherer
author_sort Andreas Tsouris
collection DOAJ
description Abstract Unraveling the genetic sources of gene expression variation is essential to better understand the origins of phenotypic diversity in natural populations. Genome-wide association studies identified thousands of variants involved in gene expression variation, however, variants detected only explain part of the heritability. In fact, variants such as low-frequency and structural variants (SVs) are poorly captured in association studies. To assess the impact of these variants on gene expression variation, we explored a half-diallel panel composed of 323 hybrids originated from pairwise crosses of 26 natural Saccharomyces cerevisiae isolates. Using short- and long-read sequencing strategies, we established an exhaustive catalog of single nucleotide polymorphisms (SNPs) and SVs for this panel. Combining this dataset with the transcriptomes of all hybrids, we comprehensively mapped SNPs and SVs associated with gene expression variation. While SVs impact gene expression variation, SNPs exhibit a higher effect size with an overrepresentation of low-frequency variants compared to common ones. These results reinforce the importance of dissecting the heritability of complex traits with a comprehensive catalog of genetic variants at the population level.
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spelling doaj.art-8a111588ffe7413683c2d11289da40b82024-04-07T11:35:05ZengSpringer NatureMolecular Systems Biology1744-42922024-02-0120436237310.1038/s44320-024-00021-0Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeastAndreas Tsouris0Gauthier Brach1Anne Friedrich2Jing Hou3Joseph Schacherer4Université de Strasbourg, CNRSUniversité de Strasbourg, CNRSUniversité de Strasbourg, CNRSUniversité de Strasbourg, CNRSUniversité de Strasbourg, CNRSAbstract Unraveling the genetic sources of gene expression variation is essential to better understand the origins of phenotypic diversity in natural populations. Genome-wide association studies identified thousands of variants involved in gene expression variation, however, variants detected only explain part of the heritability. In fact, variants such as low-frequency and structural variants (SVs) are poorly captured in association studies. To assess the impact of these variants on gene expression variation, we explored a half-diallel panel composed of 323 hybrids originated from pairwise crosses of 26 natural Saccharomyces cerevisiae isolates. Using short- and long-read sequencing strategies, we established an exhaustive catalog of single nucleotide polymorphisms (SNPs) and SVs for this panel. Combining this dataset with the transcriptomes of all hybrids, we comprehensively mapped SNPs and SVs associated with gene expression variation. While SVs impact gene expression variation, SNPs exhibit a higher effect size with an overrepresentation of low-frequency variants compared to common ones. These results reinforce the importance of dissecting the heritability of complex traits with a comprehensive catalog of genetic variants at the population level.https://doi.org/10.1038/s44320-024-00021-0eQTLDiallelLow-frequency VariantsStructural VariantsYeast
spellingShingle Andreas Tsouris
Gauthier Brach
Anne Friedrich
Jing Hou
Joseph Schacherer
Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast
Molecular Systems Biology
eQTL
Diallel
Low-frequency Variants
Structural Variants
Yeast
title Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast
title_full Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast
title_fullStr Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast
title_full_unstemmed Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast
title_short Diallel panel reveals a significant impact of low-frequency genetic variants on gene expression variation in yeast
title_sort diallel panel reveals a significant impact of low frequency genetic variants on gene expression variation in yeast
topic eQTL
Diallel
Low-frequency Variants
Structural Variants
Yeast
url https://doi.org/10.1038/s44320-024-00021-0
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