Page:Animal Cloning; A Risk Assessment (2008).pdf/4

Chapter III: Developing the Risk Assessment Methodology		41
A.	Charge	41
B.	General Discussion of Risk/Safety Analyses	41
	1. Risk and Safety	41
	2. Risk Assessment vs. Risk Management	42
C.	Risk/Safety Assessment of Cloning	42
D.	Transgenic Animal Clones	44
E.	Methodology Development	45
	1. Hazard Characterization	46
	2. Potential Risks	47
	3. Proposed Approaches	48
	a. Animal Health Risks	48
	b. Food Consumption Risks	49
F.	Two-Pronged Approach to Assessing Food Consumption Risks	50
	1. Critical Biological Systems Approach	51
	a. Overview	51
	b. Evaluation Nodes	52
G.	The Weight of Evidence Approach	54
H.	Limitations of the Risk Assessment	55
Chapter IV: Epigenetic Reprogramming: Implications for Clones and their Progeny		59
A.	Overview of Epigenetic Reprogramming in Early Embryonic Development	61
	1. Preimplantation Reprogramming	63
	a. Fusion and Cleavage	63
	b. Demethylation and Remethylation in Early Embryos	66
	c. Epigenetic Reprogramming in Later Development	70
	d. Studies of Gene Expression and Development in Clones and Animals Produced by Other ARTs	73
	e. Studies of Technical Contributions to Epigenetic Variability in Clones and Other ARTs	78
	2. Gametogenic Reprogramming	79
	3. Mitochondrial Heteroplasmy	81
	4. Conclusions from Studies of Epigenetic Reprogramming	82
B.	Phenotypic Evidence for Gametogenic Reprogramming	83
	1. Phenotypic Anomalies Observed in Mouse Clones	83
	a. Utility of Mouse Model	83
	b. Pregnancy (Developmental Node 1)	84
	c. Perinatal Period (Developmental Node 2)	86
	d. Juvenile Period to Reproductive Maturity (Developmental Nodes 3 and 4)	86
	e. Maturity and Aging (Developmental Node 5)	88
	2. Conclusions from Phenotypic Studies of Gametogenic Reprogramming in Mouse Clones and their Progeny for Reprogramming in Domestic Livestock Clones and their Progeny	90