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Linking Expressed Genome to Environment: Epigenetics

Monday, April 09, 2012

An overview of the importance of epigenetics in animal breeding and research to characterise epigentics from the final scientific report from the EU group, Sustainable Animal Breeding (SABRE) subtitled 'Cutting Edge Genomics for Sustainable Animal Breeding'.

Epigenetics refers to the study of heritable changes in genome function that occur without affecting DNA sequences. These changes result from the apposition of molecular marks that remain over several cell divisions onto the genome. Epigenetics deals with the study of how environmental factors can change the way genes are expressed.

Why important for animal breeding?

Epigenetic marks contribute to the variability of traits between individuals by governing the interactions between the expressed genome and its environment. Understanding how epigenetics can change the way genes are expressed has farreaching consequences for exploiting the variability of traits through the definition of more sustainable lowinput systems for food production. Epigenetic marks (such as DNA methylation and histone acetylation) have become amenable to high throughput analysis and have started to provide new molecular information that complements those obtained from the massive amounts of marker genotyping data. Those data are obtained from reference animal populations now used in molecular genetic testing for the selection of functional traits. By providing a readout of environmental effects, such as nutrition, climate and sanitary conditions on the animal’s expressed genome, epigenetics allows us to determine the respective contribution of genome and environment to phenotypic trait variation and shapes new frontiers in the optimization of the individual management of animals for a more environmentally and welfare friendly production.

Twin clones from the Normande Breed aft er the transfer of a single frozen embryo

Research to characterise Epigenetics

Epigenetic programming is required to develop a one-cell embryo into an adult. Variations in DNA methylation between individuals can be used to measure epigenetic variations within a population. SABRE explored late foetal growth in relation to maternal environment and relationships between early epigenetic modifications and nuclear remodeling.

Genes for intestinal functions

Pairs of homozygous twin or sets of cloned cattle provide a pertinent experimental model for a first evaluation of global epigenetic variations between genetically identical animals. Measuring the genome-wide DNA methyl content of leucocytes reveals epigenetic variations between twin genotypes, and higher variability within than between cloned genotypes. An unexpected range of 4.4% to 6.9% of DNA methyl content was found between healthy adult cattle clones (of the same genotype), demonstrating that a highly flexible DNA methylation status is associated with the functional reprogramming of a given genome into a healthy adult. Most animals developed from overgrown foetuses at birth show a global pattern of hypermethylation providing a method for determining the contribution of epigenetics to the variability of complex traits.

Epigenetics in the pig

Feeding animals with a methyl supplemented diet affected their epigenetic status by modifying the DNA methylation level of target tissues of interest (liver, muscle) and the gene regulation of a growth-related (Insulin Growth Factor, IGF) metabolic pathway. When given to pregnant sows, such a diet significantly improved growth at late foetal stages due to an impact on the expression of several of the genes. The effects of such a diet remained at the peripubertal age.

Transgenerational inheritance

When boars, which were exclusively fed with the same methyl supplemented diet, are mated with control sows, their off spring keep a higher level of DNA methylation in their muscle associated with a higher back fat thickness. Also differences in mRNA levels for muscle, liver and kidney and a trend towards a higher percentage in shoulder and adipose tissue are shown. This provocatively suggests a paternal transmission of some epimutations induced by feeding.

Further evidence of such a soft multi generational inheritance of nutrition induced epigenetic modifications to the genome is needed before exploiting individual genotype-to-epigenotype interactions in individual management of animals (diet, weaning, breeding conditions) for a more profitable and sustainable farming system.

April 2012

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