Abstract
Recent studies showed that epigenetic marks, including DNA methylation, influence production and adaptive traits in plants and animals. So far, most studies dealing with genetics and epigenetics considered DNA methylation sites independently. However, the genetic basis of the global DNA methylation rate (GDMR) remains unknown. The main objective of the present study was to investigate genetic determinism of GDMR in sheep. The experiment was conducted on 1,047 Romane sheep allocated into 10 half-sib families. After weaning, all the lambs were phenotyped for global GDMR in blood as well as for production and adaptive traits. GDMR was measured by LUminometric Methylation Analysis (LUMA) using a pyrosequencing approach. Association analyses were conducted on some of the lambs (n = 775) genotyped by using the Illumina OvineSNP50 BeadChip. Blood GDMR varied among the animals (average 70.7 ± 6.0%). Female lambs had significantly higher GDMR than male lambs. Inter-individual variability of blood GDMR had an additive genetic component and heritability was moderate (h2 = 0.20 ± 0.05). No significant genetic correlation was found between GDMR and growth or carcass traits, birthcoat, or social behaviors. Association analyses revealed 28 QTLs associated with blood GDMR. Seven genomic regions on chromosomes 1, 5, 11, 17, 24, and 26 were of most interest due to either high significant associations with GDMR or to the relevance of genes located close to the QTLs. QTL effects were moderate. Genomic regions associated with GDMR harbored several genes not yet described as being involved in DNA methylation, but some are already known to play an active role in gene expression. In addition, some candidate genes, CHD1, NCO3A, KDM8, KAT7, and KAT6A have previously been described to be involved in epigenetic modifications. In conclusion, the results of the present study indicate that blood GDMR in domestic sheep is under polygenic influence and provide new insights into DNA methylation genetic determinism.
Highlights
Genetic selection in several livestock species has recently progressed to include heritable DNA polymorphisms for the improvement of production traits (Goddard et al, 2010)
The following complete animal mixed model was fitted: y = Xβ + Zaa + Wcc + e where y is the vector of observations for the trait(s) being analyzed, β is the vector of appropriate fixed effects, a is the vector of random genetic effects and c is the vector of permanent environmental effects, when appropriate, with incidence matrices X, Za, and Wc, respectively, and e is the vector of residual effects
The global DNA methylation rate measured by LUminometric Methylation Analysis (LUMA) reached 70% in sheep blood
Summary
Genetic selection in several livestock species has recently progressed to include heritable DNA polymorphisms (i.e., genomic selection) for the improvement of production traits (Goddard et al, 2010). Particular epigenetic recombinant inbred lines of Arabidopsis thaliana showed highly variable DNA methylation, while being genetically very similar (Latzel et al, 2013) Using these plant model lines, it was demonstrated an important role of epigenetics in adaptive process facing saline conditions for example (Kooke et al, 2015). Recent advances in epigenetic studies in natural populations addressed how epigenetic inheritance may influence adaptive evolution by focusing on epigenetic stability and inheritance itself as a potentially evolving trait (Herman et al, 2014; Schlichting and Wund, 2014) These articles brought into focus the genetic and ecological basis of epigenetic stability and raised a number of questions including “is the stability of epigenetic marks heritable?”. The aim of the present study was to estimate the genetic component of the global DNA methylation rate and to identify the genomic loci underlying the phenotype
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