Cargando…
Genetics of trans-regulatory variation in gene expression
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 fo...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072440/ https://www.ncbi.nlm.nih.gov/pubmed/30014850 http://dx.doi.org/10.7554/eLife.35471 |
_version_ | 1783344019695206400 |
---|---|
author | Albert, Frank Wolfgang Bloom, Joshua S Siegel, Jake Day, Laura Kruglyak, Leonid |
author_facet | Albert, Frank Wolfgang Bloom, Joshua S Siegel, Jake Day, Laura Kruglyak, Leonid |
author_sort | Albert, Frank Wolfgang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6072440 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-60724402018-08-06 Genetics of trans-regulatory variation in gene expression Albert, Frank Wolfgang Bloom, Joshua S Siegel, Jake Day, Laura Kruglyak, Leonid eLife Chromosomes and Gene Expression 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. eLife Sciences Publications, Ltd 2018-07-17 /pmc/articles/PMC6072440/ /pubmed/30014850 http://dx.doi.org/10.7554/eLife.35471 Text en © 2018, Albert et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Chromosomes and Gene Expression Albert, Frank Wolfgang Bloom, Joshua S Siegel, Jake Day, Laura Kruglyak, Leonid Genetics of trans-regulatory variation in gene expression |
title | Genetics of trans-regulatory variation in gene expression |
title_full | Genetics of trans-regulatory variation in gene expression |
title_fullStr | Genetics of trans-regulatory variation in gene expression |
title_full_unstemmed | Genetics of trans-regulatory variation in gene expression |
title_short | Genetics of trans-regulatory variation in gene expression |
title_sort | genetics of trans-regulatory variation in gene expression |
topic | Chromosomes and Gene Expression |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6072440/ https://www.ncbi.nlm.nih.gov/pubmed/30014850 http://dx.doi.org/10.7554/eLife.35471 |
work_keys_str_mv | AT albertfrankwolfgang geneticsoftransregulatoryvariationingeneexpression AT bloomjoshuas geneticsoftransregulatoryvariationingeneexpression AT siegeljake geneticsoftransregulatoryvariationingeneexpression AT daylaura geneticsoftransregulatoryvariationingeneexpression AT kruglyakleonid geneticsoftransregulatoryvariationingeneexpression |