Abstract
Recent studies highlighted the influence of epigenetic marks in the variability of many complex traits, both in plants and animals. These studied focused only on specific sites of the genome having differentially methylated profiles among individuals and/or tissues. In contrast, we recently used the methylation rate of the entire genome as a unique measure considered as a novel quantitative phenotype in sheep. This phenotype named global DNA methylation rate (GDMR), measured by luminometric assay, integrates the methylation level of each CpG dinucleotide within the 6 million of CCGG sites along the ovine genome. GDMR measured in blood previously showed moderate heritability of 0.20 and provided evidence for a genetic determinism. The main objective of the present study was to better characterize the GDMR phenotype in various tissues and investigate its variability in several breeds of sheep reared in the same environment. GDMR was measured on blood samples collected monthly from 59 growing male and female lambs (24 Romane, 23 Blackbelly and 12 Charollais), between birth and 4 months of age. Blood GDMR was on average around 80% and was influenced by the sampling date (p < 0.001), the breed (p = 0.002) and the sex (p = 0.002). In addition, GDMR was determined in 12 somatic (frontal lobe, pituitary gland, heart, lung, sub cutaneous and perirenal adipose tissue, skeletal muscle, liver, spleen, adrenal gland, medulla and cortical kidney) and 6 reproductive tissues (ovary, oviduct, uterus, testis, epididymis and seminal vesicle). GDMR was on average 70% in somatic tissues but marked variation was observed depending on the tissue. The GDMR measured in blood was higher than that measured in other somatic tissues, and is not a good proxy of less accessible tissues. Female reproductive tissues had a 10% higher GDMR than male reproductive tissues. We demonstrated a significant influence of the breed on blood GDMR, certainly reflecting the influence of different genetic backgrounds. The effect of the breed on GDMR may be related to their specific abilities to adapt to and live in different conditions.
Highlights
Genetic improvement is widely used to increase animal production, health, and welfare in livestock systems
At slaughter, using the global DNA methylation rate (GDMR) dataset for 30 animals and 19 tissues (12 somatic tissues, three additional reproductive tissues specific to each sex and a blood sample), we looked for correlations of GDMR between tissues
The time series analysis performed in the present study indicated that GDMR of the blood was influenced by the date of sampling, a possible combined effect of age and season, but only slight GDMR changes were observed over time and the average GDMR was around 80%
Summary
Genetic improvement is widely used to increase animal production, health, and welfare in livestock systems. Epigenetic recombinant inbred lines of Arabidopsis thaliana, obtained by an initial cross of isogenic parents with different DNA methylation profiles, have provided a powerful tool to investigate the role and significance of epigenetic alteration in almost identical genetic backgrounds (Johannes et al, 2009; Latzel et al, 2013). Using these model plant lines, DNA hypomethylation of the whole genome was associated with lower resistance to increased saline environment (Kooke et al, 2015). We focused on global DNA methylation rate (GDMR) as a novel quantitative phenotype measured by pyrosequencing luminometric methylation assay (LUMA) in sheep (Hazard et al, 2020)
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