Genomic Imprinting - Imprinted Genes in Mammals

Imprinted Genes in Mammals

That imprinting might be a feature of mammalian development was suggested in breeding experiments in mice carrying reciprocal translocations. Nucleus transplantation experiments in mouse zygotes in the early 1980s confirmed that normal development requires the contribution of both the maternal and paternal genomes. The vast majority of mouse parthenogenones/gynogenones (with two maternal or egg genomes) and androgenones (with two paternal or sperm genomes) die at, or before, the blastocyst/implantation stage. In the rare instances that they develop to postimplantation stages, gynogenetic embryos show better embryonic development relative to placental development, while for androgenones, the reverse is true. Nevertheless, for the latter, only a few have been described.

Parthenogenetic/gynogenetic embryos have twice the normal expression level of maternally derived genes, and lack expression of paternally expressed genes, while the reverse is true for androgenetic embryos. It is now known that there are at least 80 imprinted genes in humans and mice, many of which are involved in embryonic and placental growth and development. Various methods have been used to identify imprinted genes. In swine, Bischoff et al. 2009 compared transcriptional profiles using short-oligonucleotide microarrays (Affymetrix Porcine GeneChip) to survey differentially expressed genes between parthenotes (2 maternal genomes) and control fetuses (1 maternal, 1 paternal genome) An intriguing study surveying the transcriptome of murine brain tissues revealed over 1300 imprinted gene loci (approximately 10-fold more than previously reported) by Illumina RNA-sequencing (RNA-Seq) technology from F1 hybrids resulting from reciprocal crosses. The result however has been challenged by others who claimed that this is an overestimation by an order of magnitude due to flawed statistical analysis.

No naturally occurring cases of parthenogenesis exist in mammals because of imprinted genes. Experimental manipulation of a paternal methylation imprint controlling the Igf2 gene has, however, recently allowed the creation of rare individual mice with two maternal sets of chromosomes - but this is not a true parthenogenone. Hybrid offspring of two species may exhibit unusual growth due to the novel combination of imprinted genes.