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Phylogenetic footprint analysis of IGF2 in extant mammals

7 October 2004: This is the first report to show that comparative footprint analysis of species from evolutionarily distant mammalian clades that exhibit a divergent imprint status is a powerful bioinformatics-based approach for identifying putative genomic motifs needed to regulate imprinting.

IGF2 was identified as an imprinted gene in mice (DeChiara et al., Nature 345: 78-80, 1990) and humans (Rainier et al., Nature 362: 747-749, 1993) over a decade ago. Since then a number of cis-acting elements required to control the reciprocal imprinting of IGF2 (paternally expressed) and the downstream H19 gene (maternally expressed) have been painstakingly identified (Murrell et al., Nat. Genet. 36: 889-893, 2004). Enhancer, silencer, and insulator motifs involved in the complex regulation of this imprinted domain were initially identified with the use of transgenic mice containing systematically produced genomic deletions and mutations (Arney, Trends Genet. 19: 17-23, 2003). Comparative sequence analysis between mouse and human has further helped in the identification of imprint control elements (Onyango et al., Genome Res. 10: 1697-1710, 2000; Engemann et al., Hum. Mol. Genet. 9: 2691-2706, 2000). Nevertheless, the usefulness of comparing orthologous imprinted regions in mice and humans is limited because high levels of interspecies sequence conservation typify animals that lie within the same Eutherian superordinal clade (Murphy et al., Nature 409: 614-618, 2001).

Weidman et al. (Genome Res. 14: 1726-1732, 2004) markedly expand these earlier IGF2 phylogenetic comparisons by including animals from the imprinted Metatherian (opossum) and non-imprinted Prototherian (platypus) subclasses of mammals (Killian et al., Mol. Cell. 5: 707-716, 2000). The full potential of this bioinformatics approach will only be fully realized once the opossum and platypus genomes are sequenced.

([Monodelphis domestica] (http://www.genome.gov/12512285)) ([Ornithorhynchus anatinus] (http://www.genome.gov/12512287))