Multiple QTL underlie milk phenotypes at the CSF2RB locus

Abstract Background Over many years, artificial selection has substantially improved milk production by cows. However, the genes that underlie milk production quantitative trait loci (QTL) remain relatively poorly characterised. Here, we investigate a previously reported QTL located at the CSF2RB lo...

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Main Authors: Thomas J. Lopdell, Kathryn Tiplady, Christine Couldrey, Thomas J. J. Johnson, Michael Keehan, Stephen R. Davis, Bevin L. Harris, Richard J. Spelman, Russell G. Snell, Mathew D. Littlejohn
Format: Article
Language:deu
Published: BMC 2019-01-01
Series:Genetics Selection Evolution
Online Access:http://link.springer.com/article/10.1186/s12711-019-0446-x
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author Thomas J. Lopdell
Kathryn Tiplady
Christine Couldrey
Thomas J. J. Johnson
Michael Keehan
Stephen R. Davis
Bevin L. Harris
Richard J. Spelman
Russell G. Snell
Mathew D. Littlejohn
author_facet Thomas J. Lopdell
Kathryn Tiplady
Christine Couldrey
Thomas J. J. Johnson
Michael Keehan
Stephen R. Davis
Bevin L. Harris
Richard J. Spelman
Russell G. Snell
Mathew D. Littlejohn
author_sort Thomas J. Lopdell
collection DOAJ
description Abstract Background Over many years, artificial selection has substantially improved milk production by cows. However, the genes that underlie milk production quantitative trait loci (QTL) remain relatively poorly characterised. Here, we investigate a previously reported QTL located at the CSF2RB locus on chromosome 5, for several milk production phenotypes, to better understand its underlying genetic and molecular causes. Results Using a population of 29,350 taurine dairy cows, we conducted association analyses for milk yield and composition traits, and identified highly significant QTL for milk yield, milk fat concentration, and milk protein concentration. Strikingly, protein concentration and milk yield appear to show co-located yet genetically distinct QTL. To attempt to understand the molecular mechanisms that might be mediating these effects, gene expression data were used to investigate eQTL for 11 genes in the broader interval. This analysis highlighted genetic impacts on CSF2RB and NCF4 expression that share similar association signatures to those observed for lactation QTL, strongly implicating one or both of these genes as responsible for these effects. Using the same gene expression dataset representing 357 lactating cows, we also identified 38 novel RNA editing sites in the 3′ UTR of CSF2RB transcripts. The extent to which two of these sites were edited also appears to be genetically co-regulated with lactation QTL, highlighting a further layer of regulatory complexity that involves the CSF2RB gene. Conclusions This locus presents a diversity of molecular and lactation QTL, likely representing multiple overlapping effects that, at a minimum, highlight the CSF2RB gene as having a causal role in these processes.
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spelling doaj.art-9e66835c202f45f5869a32d75de446502022-12-21T19:00:41ZdeuBMCGenetics Selection Evolution1297-96862019-01-0151111610.1186/s12711-019-0446-xMultiple QTL underlie milk phenotypes at the CSF2RB locusThomas J. Lopdell0Kathryn Tiplady1Christine Couldrey2Thomas J. J. Johnson3Michael Keehan4Stephen R. Davis5Bevin L. Harris6Richard J. Spelman7Russell G. Snell8Mathew D. Littlejohn9Research and Development, Livestock Improvement CorporationResearch and Development, Livestock Improvement CorporationResearch and Development, Livestock Improvement CorporationResearch and Development, Livestock Improvement CorporationResearch and Development, Livestock Improvement CorporationResearch and Development, Livestock Improvement CorporationResearch and Development, Livestock Improvement CorporationResearch and Development, Livestock Improvement CorporationSchool of Biological Sciences, University of AucklandResearch and Development, Livestock Improvement CorporationAbstract Background Over many years, artificial selection has substantially improved milk production by cows. However, the genes that underlie milk production quantitative trait loci (QTL) remain relatively poorly characterised. Here, we investigate a previously reported QTL located at the CSF2RB locus on chromosome 5, for several milk production phenotypes, to better understand its underlying genetic and molecular causes. Results Using a population of 29,350 taurine dairy cows, we conducted association analyses for milk yield and composition traits, and identified highly significant QTL for milk yield, milk fat concentration, and milk protein concentration. Strikingly, protein concentration and milk yield appear to show co-located yet genetically distinct QTL. To attempt to understand the molecular mechanisms that might be mediating these effects, gene expression data were used to investigate eQTL for 11 genes in the broader interval. This analysis highlighted genetic impacts on CSF2RB and NCF4 expression that share similar association signatures to those observed for lactation QTL, strongly implicating one or both of these genes as responsible for these effects. Using the same gene expression dataset representing 357 lactating cows, we also identified 38 novel RNA editing sites in the 3′ UTR of CSF2RB transcripts. The extent to which two of these sites were edited also appears to be genetically co-regulated with lactation QTL, highlighting a further layer of regulatory complexity that involves the CSF2RB gene. Conclusions This locus presents a diversity of molecular and lactation QTL, likely representing multiple overlapping effects that, at a minimum, highlight the CSF2RB gene as having a causal role in these processes.http://link.springer.com/article/10.1186/s12711-019-0446-x
spellingShingle Thomas J. Lopdell
Kathryn Tiplady
Christine Couldrey
Thomas J. J. Johnson
Michael Keehan
Stephen R. Davis
Bevin L. Harris
Richard J. Spelman
Russell G. Snell
Mathew D. Littlejohn
Multiple QTL underlie milk phenotypes at the CSF2RB locus
Genetics Selection Evolution
title Multiple QTL underlie milk phenotypes at the CSF2RB locus
title_full Multiple QTL underlie milk phenotypes at the CSF2RB locus
title_fullStr Multiple QTL underlie milk phenotypes at the CSF2RB locus
title_full_unstemmed Multiple QTL underlie milk phenotypes at the CSF2RB locus
title_short Multiple QTL underlie milk phenotypes at the CSF2RB locus
title_sort multiple qtl underlie milk phenotypes at the csf2rb locus
url http://link.springer.com/article/10.1186/s12711-019-0446-x
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