D. The Implications of Epigenetic Reprogramming for Clones and their Progeny (Chapter IV)
Epigenetics has been defined as the study of stable alterations in gene expression potentials that arise during development and cell proliferation. In sexual reproduction, a new diploid genome is created by the fusion of two haploid genomes. The subsequent expression of that genome into a functional organism is governed by a "program." There are several examples of epigenetic control of gene expression, of which DNA methylation is likely the best characterized.
Mammalian embryos experience major epigenetic reprogramming primarily at two times in their development, both of which have significant implications for cloning. One of these takes place soon after fertilization, and is referred to as preimplantation reprogramming; the other occurs during gametogenesis (the development of cells that ultimately become the sperm and egg). Because preimplantation reprogramming occurs after fertilization, and in the case of nuclear transfer, after fusion of the donor nucleus with the oöplast, it is the most immediately affected by the cloning process, and may be most directly implicated in the development of clones with defects. Gametogenic reprogramming may also be involved in the abnormalities noted in clones, but it likely has more far-reaching implications for progeny, because it generates the gametes used for the sexual reproduction of clones.
The efficiency of producing clones (i.e., the number of live offspring born compared to the number of embryos transferred) by SCNT is very low. The reasons for this low efficiency may be related to inappropriate epigenetic reprogramming. When cloning, the donor nucleus must be coaxed to direct embryonic development as if it were a fertilization-derived zygote. Most of the time, this is not successful. Anomalous epigenetic reprogramming is observed at the global genomic and individual gene level in clone embryos and fetuses, and in similar developmental stages of animals produced using ARTs with significant in vitro culturing components. Many of these are lethal, as demonstrated by the low success rate of IVF and the even lower success rate of SCNT. In the small number of successful cases that ultimately result in clones that appear normal and healthy, reprogramming in SCNT-derived embryos appears to be as successful as reprogramming in fertilization-derived embryos. Live and apparently healthy clones may exhibit some level of epigenetic differences relative to fertilization-derived animals, but these differences do not appear to have adverse effects on their well-being or ability to grow and develop normally.
The Center assumes that if clones were to pose food consumption risks, the only mechanism by which those risks could arise would be from inappropriate epigenetic reprogramming, similar to those observed for other ARTs. It is important to note that the genes that are being dysregulated are the "normal," naturally present genes that comprise the animal's genome, and have not been
Animal Cloning: A Risk Assessment
