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Cloning and in vitro culture of sheep embryos have been associated with bigger livestock and 'large offspring syndrome' (LOS). In the February Nature Genetics Young et al. provide a molecular explanation for the observed fetal overgrowth (Nat Genet 2001, 27:153-154). They developed a culture system that consistently results in large offspring (LO) in 25% of births. Young et al. measured the levels of several imprinted genes that are associated with fetal overgrowth syndromes in man. The levels of IGFR2 mRNA were reduced by 30-60% in LO embryos and protein levels were diminished by as much as 60-80%. Reduced IGF2R expression was associated with loss of methylation of the differentially methylated region from the second intron of the ovine IGF2R gene. These results suggest an epigenetic mechanism for the LOS overgrowth phenotype.

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