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Genomic Imprinting

With respect to the primary genome sequence, it does not make a difference whether an allele is inherited by the mother or the father. As opposed to that, the inheritance of epigenetic DNA-modifications, predominantly methylation, often underlies a so-called imprinting. This is, the offspring cell distinguishes between the maternally and the paternally inherited allele by means of the different methylation patterns. Thus, the phenotype of the offspring depends on the sex of the parent who has inherited an imprinted allele due to promoter inhibition of one allele by DNA-methylation. A well studied example is the cross-breeding of donkey and horse. Here, the progeny of a female donkey and a male horse are mules, whereas a female horse and a male donkey give birth to hinnies.














The evolution of imprinting is yet unclear, but one hypothesis indicates imprinting as genetic "battle of the sexes," since many imprinted genes regulate embryonic growth. Maternally-expressed imprinted genes (i.e. solely the maternally inherited allele is expressed) usually suppress growth (e.g. insulin like growth factor receptor 2, Igf2r), while paternally expressed imprinted genes usually enhance growth (e.g. Igf2). This might be a biological strategy to balance the size of the foetus, limited by the sizes of uterus, birth canal and pelvis.













Due to their regulatory role of growth and ontogenesis, imprinted genes likely are crucial in the development of cancer and other growth and developmental aberrations of cells and tissues (e.g. birth defects, Beckwith-Wiedemann syndrome, Prader-Willi syndrome, Angelman syndrome).
Some types of cancer are caused by the erroneous promoter inhibition of maternally imprinted tumour suppressor genes. On the other hand, many oncogenes - growth-promoting genes - are paternally imprinted genes. They are required for proper cell growth, proliferation and differentiation. However, if the maternal copy of the oncogene loses its epigenetic (methylation) labels and expression, thus, is activated, accelerated and uncontrolled cell proliferation may be the consequence. Yet, first promising strategies aiming to alter methylation patterns and imprinting of oncogenes (Memorial Sloan Kettering Acute Leukaemia) have been designed.


Still, researchers are on the way to understand the mechanisms of imprinting and the regulation of imprinting labelling. In sperm and egg, for instance, imprinted alleles have to be re-imprinted. Thus, a paternally imprinted allele inherited by a father to his daughter (the copy is paternally inherited and will be "turned on") and then to her child (it's now a maternally inherited copy and will be "turned off").



Genomic imprinting is probably responsible for hereditary defects caused by in-vitro fertilisation and cloning of mammals (e.g. "Dolly" born with a vast burden of false epigenetic information due to sole maternal imprinting). Children born after conception with the help of "Assisted Reproductive Technologies" (ARTs) showed significant lower birth weight, a higher incidence of juvenile cancer and an increased frequency of Beckwith-Wiedemann and Angelman syndrome, respectively (Schieve et al., Obstet. Gynecol 2004; Gosden et al., Lancet 2003; Niemetz and Feinberg Am J Hum Genet 2004).






For further information visit:
The genomic imprinting website
The University of Florida
The Johns Hopkins Hospital
Maher ER et al. Epigenetic risks related to assisted reproductive technologies: Epigenetics, imprinting, ART and icebergs? Hum. Reprod. (2003) 18 (12): 2508-2511.