Cloning, a term originally used primarily in horticulture to describe asexually produced progeny, means to make a copy of an individual organism, or in cellular and molecular biology, groups of identical cells and replicas of DNA and other molecules. For example, monozygotic twins are clones. Although clone is descriptive for multiple approaches for cloning animals, in this report clone is used as a descriptor for somatic cell nuclear transfer.
Animal cloning during the late 1980s resulted from the transfer of nuclei from blastomeres of early cleavage-stage embryos into enucleated oocytes, and cloning of livestock and laboratory animals has resulted from transferring a nucleus from a somatic cell into an oocyte from which the nucleus has been removed (Westhusin et al., 2001; Wilmut et al., 1997).
Somatic cell nuclear transfer can also be used to produce undifferentiated embryonic stem cells, which are matched to the recipient for research and therapy that is independent of the reproductive cloning of animals. The progeny from cloning using nuclei from either blastomeres or somatic cells are not exact replicas of an individual animal due to cytoplasmic inheritance of mitochondrial DNA from the donor egg, other cytoplasmic factors that may influence “reprogramming” of the genome of the transferred nucleus, and subsequent development of the cloned organism (Cummins, 2001; Jaenisch and Wilmut, 2001).
Cloning by nuclear transfer from embryonic blastomeres (Willadsen, 1989; Willadsen and Polge, 1981) or from a differentiated cell of an adult (Kuhholzer and Prather, 2000; Polejaeva et al., 2000; Wilmut et al., 1997) requires that the introduced nucleus be reprogrammed by the cytoplasm of the egg and direct development of a new embryo, which is then transferred to a recipient mother for development to term. The offspring will be identical to their siblings and to the original donor animal in terms of their nuclear DNA, but will differ in their mitochondrial genes; variances in the manner nuclear genes are expressed are also possible.
Epigenetics is the study of factors that influence behavior of a cell without directly affecting its DNA or other genetic components. The epigenetic view of differentiation is that cells undergo differentiation events that depend on correct temporal and spatial repression, derepression, or activation of genes affecting the fate of cells, tissues, organs, and ultimately, organisms. Thus epigenetic changes in an organism are normal and result in alterations in gene expression. For example, epigenetic transformation of a normal cell to a tumor cell can occur without mutation of any gene.