Expression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus.

Milk is composed of a complex mixture of lipids, proteins, carbohydrates and various vitamins and minerals as a source of nutrition for young mammals. The composition of milk varies between individuals, with lipid composition in particular being highly heritable. Recent reports have highlighted a re...

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Autores principales:	Mathew D Littlejohn, Kathryn Tiplady, Thomas Lopdell, Tania A Law, Andrew Scott, Chad Harland, Ric Sherlock, Kristen Henty, Vlad Obolonkin, Klaus Lehnert, Alistair Macgibbon, Richard J Spelman, Stephen R Davis, Russell G Snell
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2014
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f633f8df1ee74cb8afd54206aa3509bb
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spelling	oai:doaj.org-article:f633f8df1ee74cb8afd54206aa3509bb2021-11-18T08:36:58ZExpression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus.1932-620310.1371/journal.pone.0085757https://doaj.org/article/f633f8df1ee74cb8afd54206aa3509bb2014-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24465687/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Milk is composed of a complex mixture of lipids, proteins, carbohydrates and various vitamins and minerals as a source of nutrition for young mammals. The composition of milk varies between individuals, with lipid composition in particular being highly heritable. Recent reports have highlighted a region of bovine chromosome 27 harbouring variants affecting milk fat percentage and fatty acid content. We aimed to further investigate this locus in two independent cattle populations, consisting of a Holstein-Friesian x Jersey crossbreed pedigree of 711 F2 cows, and a collection of 32,530 mixed ancestry Bos taurus cows. Bayesian genome-wide association mapping using markers imputed from the Illumina BovineHD chip revealed a large quantitative trait locus (QTL) for milk fat percentage on chromosome 27, present in both populations. We also investigated a range of other milk composition phenotypes, and report additional associations at this locus for fat yield, protein percentage and yield, lactose percentage and yield, milk volume, and the proportions of numerous milk fatty acids. We then used mammary RNA sequence data from 212 lactating cows to assess the transcript abundance of genes located in the milk fat percentage QTL interval. This analysis revealed a strong eQTL for AGPAT6, demonstrating that high milk fat percentage genotype is also additively associated with increased expression of the AGPAT6 gene. Finally, we used whole genome sequence data from six F1 sires to target a panel of novel AGPAT6 locus variants for genotyping in the F2 crossbreed population. Association analysis of 58 of these variants revealed highly significant association for polymorphisms mapping to the 5'UTR exons and intron 1 of AGPAT6. Taken together, these data suggest that variants affecting the expression of AGPAT6 are causally involved in differential milk fat synthesis, with pleiotropic consequences for a diverse range of other milk components.Mathew D LittlejohnKathryn TipladyThomas LopdellTania A LawAndrew ScottChad HarlandRic SherlockKristen HentyVlad ObolonkinKlaus LehnertAlistair MacgibbonRichard J SpelmanStephen R DavisRussell G SnellPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 9, Iss 1, p e85757 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mathew D Littlejohn Kathryn Tiplady Thomas Lopdell Tania A Law Andrew Scott Chad Harland Ric Sherlock Kristen Henty Vlad Obolonkin Klaus Lehnert Alistair Macgibbon Richard J Spelman Stephen R Davis Russell G Snell Expression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus.
description	Milk is composed of a complex mixture of lipids, proteins, carbohydrates and various vitamins and minerals as a source of nutrition for young mammals. The composition of milk varies between individuals, with lipid composition in particular being highly heritable. Recent reports have highlighted a region of bovine chromosome 27 harbouring variants affecting milk fat percentage and fatty acid content. We aimed to further investigate this locus in two independent cattle populations, consisting of a Holstein-Friesian x Jersey crossbreed pedigree of 711 F2 cows, and a collection of 32,530 mixed ancestry Bos taurus cows. Bayesian genome-wide association mapping using markers imputed from the Illumina BovineHD chip revealed a large quantitative trait locus (QTL) for milk fat percentage on chromosome 27, present in both populations. We also investigated a range of other milk composition phenotypes, and report additional associations at this locus for fat yield, protein percentage and yield, lactose percentage and yield, milk volume, and the proportions of numerous milk fatty acids. We then used mammary RNA sequence data from 212 lactating cows to assess the transcript abundance of genes located in the milk fat percentage QTL interval. This analysis revealed a strong eQTL for AGPAT6, demonstrating that high milk fat percentage genotype is also additively associated with increased expression of the AGPAT6 gene. Finally, we used whole genome sequence data from six F1 sires to target a panel of novel AGPAT6 locus variants for genotyping in the F2 crossbreed population. Association analysis of 58 of these variants revealed highly significant association for polymorphisms mapping to the 5'UTR exons and intron 1 of AGPAT6. Taken together, these data suggest that variants affecting the expression of AGPAT6 are causally involved in differential milk fat synthesis, with pleiotropic consequences for a diverse range of other milk components.
format	article
author	Mathew D Littlejohn Kathryn Tiplady Thomas Lopdell Tania A Law Andrew Scott Chad Harland Ric Sherlock Kristen Henty Vlad Obolonkin Klaus Lehnert Alistair Macgibbon Richard J Spelman Stephen R Davis Russell G Snell
author_facet	Mathew D Littlejohn Kathryn Tiplady Thomas Lopdell Tania A Law Andrew Scott Chad Harland Ric Sherlock Kristen Henty Vlad Obolonkin Klaus Lehnert Alistair Macgibbon Richard J Spelman Stephen R Davis Russell G Snell
author_sort	Mathew D Littlejohn
title	Expression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus.
title_short	Expression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus.
title_full	Expression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus.
title_fullStr	Expression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus.
title_full_unstemmed	Expression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus.
title_sort	expression variants of the lipogenic agpat6 gene affect diverse milk composition phenotypes in bos taurus.
publisher	Public Library of Science (PLoS)
publishDate	2014
url	https://doaj.org/article/f633f8df1ee74cb8afd54206aa3509bb
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Expression variants of the lipogenic AGPAT6 gene affect diverse milk composition phenotypes in Bos taurus.

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