Cloning livestock.

An efficient animal cloning technology, using the procedure of nuclear transfer (NT), would provide many new opportunities for livestock agriculture, animal conservation and biomedicine. Although it is 10 years since the birth of ‘Dolly’, the first animal to be cloned from an adult cell, it is still remarkable that NT using differentiated donor cells can produce physiologically normal cloned animals. But the process is very inefficient, poorly understood and appears highly prone to epigenetic errors. With the present technology, only up to 6% of the embryos transferred to the reproductive tracts of recipient females typically result in long-term surviving clones. Not only are there high losses throughout gestation, during birth and in the immediate post-natal period, but also throughout adulthood. Many of the pregnancy losses relate to failure of the placenta to develop and function correctly. Placental dysfunction may also have an adverse influence on postnatal viability and health. These anomalies are probably due to incorrect epigenetic reprogramming of the donor genome following NT, leading to inappropriate patterns of gene expression during the development of clones. While some physiological tests on surviving clones suggest normality, other reports indicate a variety of post-natal clone-associated abnormalities. Importantly, it appears that these clone-associated phenotypes are not transmitted to offspring following sexual reproduction. This indicates that they represent epigenetic errors which are corrected during gametogenesis. While this requires molecular confirmation, it provides initial confidence in the first application of NT in agriculture, namely, the production of small numbers of cloned sires from genetically elite males, for natural mating, to effectively disseminate genetic gain. Considerably more efficient cloning methods will be required for large-scale dissemination of whole genotypes of elite livestock from nucleus herds directly to commercial producers. The continual advances in animal genomics towards the identification of genes that influence livestock production traits and human health serve to increase the ability to genetically modify cultured cells, prior to NT, to generate livestock with increased productivity or that produce superior quality food and biomedical products for niche markets. The potential opportunities for animal agriculture are more challenging because of the greater demands on cost, efficiency, consumer acceptance and relative value of the product to be viable in contrast to biomedical applications. Hence, the integration of this technology into practical farming systems remains some time in the future.