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Antagonistic Growth Promoting Effects of Imprinted Genes

14 January 2015: Imprinted genes are monoallelic expressed in a parent-of-origin dependent manner (Jirtle and Weidman 2007).The conflict theory of genomic imprinting predicts that maternally expressed genes are antigrowth while paternally expressed genes are progrowth (Haig and Graham 1991). The first two genes experimentally identified to be imprinted, the maternally expressed Igf2r (Barlow et al. 1991) and the paternally expressed Igf2 (DeChiara et al. 1991), were shown over two decades ago to adhere to this prediction. A second set of oppositely imprinted, fetal growth antagonistic genes has now been identified, the maternally expressed Grb10 and the paternally expressed Dlk1 (Madon-Simon et al. 2014). Grb10 encodes for an intracellular signaling adaptor protein that restricts fetal growth and promotes fat deposition. In contrast, Dlk1 encodes for a ligand that promotes fetal growth and restricts fat deposition. Deregulation of DLK1 expression by a single point mutation also results in the muscle hypertrophic, callipyge (i.e. beautiful buttock) phenotype in sheep (Freking et al. 2002). Thus, there may be an evolutionary conflict between genes of maternal and paternal origin over the optimal proportions of body fat and lean muscle mass (Haig 2014).