We all inherit two copies of every autosomal gene, one copy from our mother and one from our father. Both copies are functional for the majority of these genes; however, in a small subset one copy is turned off in a parent-of-origin dependent manner. These genes are called 'imprinted' because one copy of the gene was epigenetically marked or imprinted in either the egg or the sperm. Thus, the allelic expression of an imprinted gene depends upon whether it resided in a male or female the previous generation. Imprinted expression can also vary between tissues, developmental stages, and species (Reik and Walter, Genomic imprinting: parental influence on the genome. Nat Rev Genet 2: 21-32, 2001).
The phenomenon of genomic imprinting evolved in a common ancestor to marsupials and eutherian mammals over 150 million years ago (Killian et al, M6P/IGF2R imprinting evolution in mammals. Mol Cell 5: 707-716, 2000). Thus, genomic imprinting evolved in mammals with the advent of live birth. Its evolution apparently occurred because of a parental battle between the sexes to control the maternal expenditure of resources to the offspring (Haig, Altercation of generations: genetic conflicts of pregnancy. Am J Reprod Immunol 35: 226-232, 1996). Paternally expressed imprinted genes tend to promote growth while it is suppressed by those genes that are maternally expressed. Thus, paternally expressed genes enhance the extraction of nutrients from the mother during pregnancy, whereas, the maternal genome seeks to limit it. This genetic battle between the mother and father appears to continue even after birth since mice that lack paternally expressed Peg1 (Lefebvre et al, Abnormal maternal behaviour and growth retardation associated with loss of the imprinted gene Mest. Nat Genet : 163-169, 1998) and Peg3 (Li et al, Regulation of maternal behavior and offspring growth by paternally expressed Peg3. Science 284: 330-333, 1999) have reduced maternal nurturing behavior.
Imprinted genes are susceptibility targets for numerous human pathologies because their functional haploid state enables a single genomic or epigenomic change to dysregulate their function causing potentially disastrous health effects. Imprinting anomalies are often manifested as developmental and neurological disorders when they occur during early development, and as cancer when altered later in life. Specifically, imprinting disorders have been linked to Angelman and Prader-Willi Syndromes, Alzheimer disease, autism, bipolar disorder, diabetes, male sexual orientation, obesity, and schizophrenia; as well as a number of cancers: bladder, breast, cervical, colorectal, esophageal, hepatocellular, lung, mesothelioma, ovarian, prostate, testicular, and leukemia, among others (Falls et al, Genomic Imprinting: Implications for human disease. Am J Pathol 154: 635-47, 1999; Jirtle, Genomic imprinting and cancer. Exp Cell Res 248: 18-24, 1999).
The mechanisms for imprinting are still incompletely defined, but they involve epigenetic modifications that are erased and then reset during the creation of eggs and sperm. Recent research shows that maternal methyl deficient diets during pregnancy can alter the expression of imprinted genes in the offspring (Waterland et al, Post-weaning diet affects genomic imprinting at the insulin-like growth factor 2 (Igf2) locus. Hum Mol Genet 15: 705-716, 2006). This makes imprinted genes likely epigenetic targets for environmental interactions with the genome. Moreover, because imprinted genes vary significantly between species, they must not only be identified in mice (Luedi et al, Genome-wide prediction of imprinted murine genes. Genome Res 15: 875-884, 2005), but also in humans if we are going to understand human diseases and the impact of chemical and physical agents in their etiology.