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 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.
Research & Development, Livestock Improvement Corporation, Hamilton, New Zealand.
Mathew D
MD
Littlejohn
Research & Development, Livestock Improvement Corporation, Hamilton, New Zealand.
Kathryn
K
Tiplady
Research & Development, Livestock Improvement Corporation, Hamilton, New Zealand.
Thomas
T
Lopdell
School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Tania A
TA
Law
Research & Development, Livestock Improvement Corporation, Hamilton, New Zealand.
Andrew
A
Scott
Research & Development, Livestock Improvement Corporation, Hamilton, New Zealand.
Chad
C
Harland
Research & Development, Livestock Improvement Corporation, Hamilton, New Zealand.
Ric
R
Sherlock
Research & Development, Livestock Improvement Corporation, Hamilton, New Zealand ; School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Kristen
K
Henty
Research & Development, Livestock Improvement Corporation, Hamilton, New Zealand.
Vlad
V
Obolonkin
Research & Development, Livestock Improvement Corporation, Hamilton, New Zealand ; School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Klaus
K
Lehnert
Nutrition and Bioactives, Fonterra Research Centre, Palmerston North, New Zealand.
Alistair
A
Macgibbon
Research & Development, Livestock Improvement Corporation, Hamilton, New Zealand.
Richard J
RJ
Spelman
Research & Development, Livestock Improvement Corporation, Hamilton, New Zealand.
Stephen R
SR
Davis
School of Biological Sciences, University of Auckland, Auckland, New Zealand.
Russell G
RG
Snell
D000818:Animals; D001483:Base Sequence; D002417:Cattle / Q000235:genetics*; D033481:Chromosomes, Mammalian / Q000235:genetics; D003433:Crosses, Genetic; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000235:genetics*; D007774:Lactation / Q000235:genetics; D008055:Lipids / Q000235:genetics; D050155:Lipogenesis / Q000235:genetics*; D008297:Male; D008321:Mammary Glands, Animal / Q000378:metabolism; D008892:Milk / Q000378:metabolism*; D008969:Molecular Sequence Data; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D008055:Lipids; D012333:RNA, Messenger; D005992:Glycerol-3-Phosphate O-Acyltransferase