Abstract
BackgroundMilk yield for Holstein cows has doubled over five decades due to genetic selection and changes to management, but the molecular mechanisms that facilitated this increase are mostly unknown. Epigenetic modifications to the cattle genome are a plausible molecular mechanism to cause variation in milk yield and our objective was to describe genome-wide DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from mature Holstein dairy cows with variable milk yield.ResultsWhole genome MeDIP-seq was performed following DNA extraction from PBMC of 6 lactating dairy cows from 4 different herds that varied in milk yield from 13,556 kg to 23,105 kg per 305 day lactation. We describe methylation across the genome and for 13,677 protein coding genes. Repetitive element reads were primarily mapped to satellite (36.4%), SINE (29.1%), and LINE (23.7%) regions and the majority (78.4%) of CpG sites were sequenced at least once. DNA methylation was generally low upstream of genes with the nadir occurring 95 bp prior to the transcription start site (TSS). Methylation was lower in the first exon than in later exons, was highest for introns near the intron-exon junctions, and declined downstream as the distance from the gene increased. We identified 72 differentially methylated regions (DMR) between high milk yield cows and their control, and 252 DMR across herd environments.ConclusionsThis reference methylome for cattle with extreme variation in milk yield phenotype provides a resource to more fully evaluate relationships between DNA methylation and phenotype in populations subject to selection. The detection of DMR in cows of varying milk yield suggests potential to exploit epigenetic variation in cattle improvement programs.
Highlights
Milk yield for Holstein cows has doubled over five decades due to genetic selection and changes to management, but the molecular mechanisms that facilitated this increase are mostly unknown
The intermediate milk yield cows were from farms that allowed pasture access for lactating cows during the summer, whereas the case-control cows remained confined during lactation
Identifying cows with extremely high milk yield required that we sample cows from generally well-managed herds; our control cows had milk yield that was somewhat higher than the national average of 12,087 kg for Holsteins [3]
Summary
Milk yield for Holstein cows has doubled over five decades due to genetic selection and changes to management, but the molecular mechanisms that facilitated this increase are mostly unknown. Epigenetic modifications to the cattle genome are a plausible molecular mechanism to cause variation in milk yield and our objective was to describe genome-wide DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from mature Holstein dairy cows with variable milk yield. Molecular mechanisms that confer phenotypic diversity and that facilitate selective change include DNA methylation [1]. Changes to cow housing, feeding, and management have increased milk yield by an additional 2503 kg, with the combined effect of genetic selection and management resulting in an approximate doubling of milk yield in five decades.
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