Expression Variants of the Lipogenic AGPAT6 Gene Affect Diverse Milk Composition Phenotypes in Bos taurus

Abstract

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.

Polymorphisms in lipogenic genes and milk fatty acid composition in Holstein dairy cattle

“…t7:20 † Significance was declared if P-value was ≤ 0.005 after applying Bonferroni adjustment (0.05 divided by the number of comparisons that was 10).possible that one of the main functions of AGPAT6 might be phospholipid biosynthesis for milk fat globule membranes. This claim is supported by recent determinations of AGPAT6 as a candidate gene for milk fat percentage QTL in dairy cattle[28,52]. In our study, however, there were no significant association between AGPAT6 polymorphisms and milk fat percentage.…”

“…suggested that genetically these phenotypes can be considered as the 460 same trait [16]. Polymorphisms in AGPAT6 were also associated with 461 milk plamitic acid concentration [28]. There were no significant associ-462 ations between AGPAT6 haplotypes and milk FA composition deter-463 mined in our study.…”

MicroRNA-26a/b and their host genes synergistically regulate triacylglycerol synthesis by targeting theINSIG1gene

“…Both DGAT1 and AGPAT6 are key components of the overall pathway leading to synthesis of milk lipid droplets and affect milk fat yield and composition. 42 , 41 , 33 Although the expression of AGPAT6 did not change, the fact that overexpression of miR-26a/b and their host genes had a significant effect on DGAT1 mRNA expression provides evidence of a mechanistic link between the miRNA and the process of desaturation and esterification…”

Tissues, Metabolic Pathways and Genes of Key Importance in Lactating Dairy Cattle

“…The transcription rate of GPAT4 is highly correlated with concentrations of diacylglycerols and triacylglycerols in milk [9,15]. In a more recent study, this region on chromosome 27 was reported for associations with milk fat and milk volume, protein and lactose content in Holstein and Jersey crossbreds [92]. Mullen et al [110] have detected several novel and previously identified associations involving variants within introns of the IGF1 gene associated with milk protein yield, milk fat yield, milk fat concentration, somatic cell score and carcass associated traits in Holstein dairy cattle [110].…”