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Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues

Genetic variants which affect complex traits (causal variants) are thought to be found in functional regions of the genome. Identifying causal variants would be useful for predicting complex trait phenotypes in dairy cows, however, functional regions are poorly annotated in the bovine genome. Functi...

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Autores principales: Prowse-Wilkins, Claire P., Wang, Jianghui, Xiang, Ruidong, Garner, Josie B., Goddard, Michael E., Chamberlain, Amanda J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260860/
https://www.ncbi.nlm.nih.gov/pubmed/34249087
http://dx.doi.org/10.3389/fgene.2021.664379
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author Prowse-Wilkins, Claire P.
Wang, Jianghui
Xiang, Ruidong
Garner, Josie B.
Goddard, Michael E.
Chamberlain, Amanda J.
author_facet Prowse-Wilkins, Claire P.
Wang, Jianghui
Xiang, Ruidong
Garner, Josie B.
Goddard, Michael E.
Chamberlain, Amanda J.
author_sort Prowse-Wilkins, Claire P.
collection PubMed
description Genetic variants which affect complex traits (causal variants) are thought to be found in functional regions of the genome. Identifying causal variants would be useful for predicting complex trait phenotypes in dairy cows, however, functional regions are poorly annotated in the bovine genome. Functional regions can be identified on a genome-wide scale by assaying for post-translational modifications to histone proteins (histone modifications) and proteins interacting with the genome (e.g., transcription factors) using a method called Chromatin immunoprecipitation followed by sequencing (ChIP-seq). In this study ChIP-seq was performed to find functional regions in the bovine genome by assaying for four histone modifications (H3K4Me1, H3K4Me3, H3K27ac, and H3K27Me3) and one transcription factor (CTCF) in 6 tissues (heart, kidney, liver, lung, mammary and spleen) from 2 to 3 lactating dairy cows. Eighty-six ChIP-seq samples were generated in this study, identifying millions of functional regions in the bovine genome. Combinations of histone modifications and CTCF were found using ChromHMM and annotated by comparing with active and inactive genes across the genome. Functional marks differed between tissues highlighting areas which might be particularly important to tissue-specific regulation. Supporting the cis-regulatory role of functional regions, the read counts in some ChIP peaks correlated with nearby gene expression. The functional regions identified in this study were enriched for putative causal variants as seen in other species. Interestingly, regions which correlated with gene expression were particularly enriched for potential causal variants. This supports the hypothesis that complex traits are regulated by variants that alter gene expression. This study provides one of the largest ChIP-seq annotation resources in cattle including, for the first time, in the mammary gland of lactating cows. By linking regulatory regions to expression QTL and trait QTL we demonstrate a new strategy for identifying causal variants in cattle.
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spelling pubmed-82608602021-07-08 Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues Prowse-Wilkins, Claire P. Wang, Jianghui Xiang, Ruidong Garner, Josie B. Goddard, Michael E. Chamberlain, Amanda J. Front Genet Genetics Genetic variants which affect complex traits (causal variants) are thought to be found in functional regions of the genome. Identifying causal variants would be useful for predicting complex trait phenotypes in dairy cows, however, functional regions are poorly annotated in the bovine genome. Functional regions can be identified on a genome-wide scale by assaying for post-translational modifications to histone proteins (histone modifications) and proteins interacting with the genome (e.g., transcription factors) using a method called Chromatin immunoprecipitation followed by sequencing (ChIP-seq). In this study ChIP-seq was performed to find functional regions in the bovine genome by assaying for four histone modifications (H3K4Me1, H3K4Me3, H3K27ac, and H3K27Me3) and one transcription factor (CTCF) in 6 tissues (heart, kidney, liver, lung, mammary and spleen) from 2 to 3 lactating dairy cows. Eighty-six ChIP-seq samples were generated in this study, identifying millions of functional regions in the bovine genome. Combinations of histone modifications and CTCF were found using ChromHMM and annotated by comparing with active and inactive genes across the genome. Functional marks differed between tissues highlighting areas which might be particularly important to tissue-specific regulation. Supporting the cis-regulatory role of functional regions, the read counts in some ChIP peaks correlated with nearby gene expression. The functional regions identified in this study were enriched for putative causal variants as seen in other species. Interestingly, regions which correlated with gene expression were particularly enriched for potential causal variants. This supports the hypothesis that complex traits are regulated by variants that alter gene expression. This study provides one of the largest ChIP-seq annotation resources in cattle including, for the first time, in the mammary gland of lactating cows. By linking regulatory regions to expression QTL and trait QTL we demonstrate a new strategy for identifying causal variants in cattle. Frontiers Media S.A. 2021-06-23 /pmc/articles/PMC8260860/ /pubmed/34249087 http://dx.doi.org/10.3389/fgene.2021.664379 Text en Copyright © 2021 Prowse-Wilkins, Wang, Xiang, Garner, Goddard and Chamberlain. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Genetics
Prowse-Wilkins, Claire P.
Wang, Jianghui
Xiang, Ruidong
Garner, Josie B.
Goddard, Michael E.
Chamberlain, Amanda J.
Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues
title Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues
title_full Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues
title_fullStr Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues
title_full_unstemmed Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues
title_short Putative Causal Variants Are Enriched in Annotated Functional Regions From Six Bovine Tissues
title_sort putative causal variants are enriched in annotated functional regions from six bovine tissues
topic Genetics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260860/
https://www.ncbi.nlm.nih.gov/pubmed/34249087
http://dx.doi.org/10.3389/fgene.2021.664379
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