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Transcriptome-Wide Association Supplements Genome-Wide Association in Zea mays
Modern improvement of complex traits in agricultural species relies on successful associations of heritable molecular variation with observable phenotypes. Historically, this pursuit has primarily been based on easily measurable genetic markers. The recent advent of new technologies allows assaying...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Genetics Society of America
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723120/ https://www.ncbi.nlm.nih.gov/pubmed/31337639 http://dx.doi.org/10.1534/g3.119.400549 |
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author | Kremling, Karl A. G. Diepenbrock, Christine H. Gore, Michael A. Buckler, Edward S. Bandillo, Nonoy B. |
author_facet | Kremling, Karl A. G. Diepenbrock, Christine H. Gore, Michael A. Buckler, Edward S. Bandillo, Nonoy B. |
author_sort | Kremling, Karl A. G. |
collection | PubMed |
description | Modern improvement of complex traits in agricultural species relies on successful associations of heritable molecular variation with observable phenotypes. Historically, this pursuit has primarily been based on easily measurable genetic markers. The recent advent of new technologies allows assaying and quantifying biological intermediates (hereafter endophenotypes) which are now readily measurable at a large scale across diverse individuals. The usefulness of endophenotypes for delineating the regulatory landscape of the genome and genetic dissection of complex trait variation remains underexplored in plants. The work presented here illustrated the utility of a large-scale (299-genotype and seven-tissue) gene expression resource to dissect traits across multiple levels of biological organization. Using single-tissue- and multi-tissue-based transcriptome-wide association studies (TWAS), we revealed that about half of the functional variation acts through altered transcript abundance for maize kernel traits, including 30 grain carotenoid abundance traits, 20 grain tocochromanol abundance traits, and 22 field-measured agronomic traits. Comparing the efficacy of TWAS with genome-wide association studies (GWAS) and an ensemble approach that combines both GWAS and TWAS, we demonstrated that results of TWAS in combination with GWAS increase the power to detect known genes and aid in prioritizing likely causal genes. Using a variance partitioning approach in the largely independent maize Nested Association Mapping (NAM) population, we also showed that the most strongly associated genes identified by combining GWAS and TWAS explain more heritable variance for a majority of traits than the heritability captured by the random genes and the genes identified by GWAS or TWAS alone. This not only improves the ability to link genes to phenotypes, but also highlights the phenotypic consequences of regulatory variation in plants. |
format | Online Article Text |
id | pubmed-6723120 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
spelling | pubmed-67231202019-09-17 Transcriptome-Wide Association Supplements Genome-Wide Association in Zea mays Kremling, Karl A. G. Diepenbrock, Christine H. Gore, Michael A. Buckler, Edward S. Bandillo, Nonoy B. G3 (Bethesda) Investigations Modern improvement of complex traits in agricultural species relies on successful associations of heritable molecular variation with observable phenotypes. Historically, this pursuit has primarily been based on easily measurable genetic markers. The recent advent of new technologies allows assaying and quantifying biological intermediates (hereafter endophenotypes) which are now readily measurable at a large scale across diverse individuals. The usefulness of endophenotypes for delineating the regulatory landscape of the genome and genetic dissection of complex trait variation remains underexplored in plants. The work presented here illustrated the utility of a large-scale (299-genotype and seven-tissue) gene expression resource to dissect traits across multiple levels of biological organization. Using single-tissue- and multi-tissue-based transcriptome-wide association studies (TWAS), we revealed that about half of the functional variation acts through altered transcript abundance for maize kernel traits, including 30 grain carotenoid abundance traits, 20 grain tocochromanol abundance traits, and 22 field-measured agronomic traits. Comparing the efficacy of TWAS with genome-wide association studies (GWAS) and an ensemble approach that combines both GWAS and TWAS, we demonstrated that results of TWAS in combination with GWAS increase the power to detect known genes and aid in prioritizing likely causal genes. Using a variance partitioning approach in the largely independent maize Nested Association Mapping (NAM) population, we also showed that the most strongly associated genes identified by combining GWAS and TWAS explain more heritable variance for a majority of traits than the heritability captured by the random genes and the genes identified by GWAS or TWAS alone. This not only improves the ability to link genes to phenotypes, but also highlights the phenotypic consequences of regulatory variation in plants. Genetics Society of America 2019-07-23 /pmc/articles/PMC6723120/ /pubmed/31337639 http://dx.doi.org/10.1534/g3.119.400549 Text en Copyright © 2019 Kremling et al. http://creativecommons.org/licenses/by/4.0 This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigations Kremling, Karl A. G. Diepenbrock, Christine H. Gore, Michael A. Buckler, Edward S. Bandillo, Nonoy B. Transcriptome-Wide Association Supplements Genome-Wide Association in Zea mays |
title | Transcriptome-Wide Association Supplements Genome-Wide Association in Zea mays |
title_full | Transcriptome-Wide Association Supplements Genome-Wide Association in Zea mays |
title_fullStr | Transcriptome-Wide Association Supplements Genome-Wide Association in Zea mays |
title_full_unstemmed | Transcriptome-Wide Association Supplements Genome-Wide Association in Zea mays |
title_short | Transcriptome-Wide Association Supplements Genome-Wide Association in Zea mays |
title_sort | transcriptome-wide association supplements genome-wide association in zea mays |
topic | Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723120/ https://www.ncbi.nlm.nih.gov/pubmed/31337639 http://dx.doi.org/10.1534/g3.119.400549 |
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