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Genomic imprinting and the parent of origin effect.
Genomic imprinting and the parent of origin effect.

Genomic imprinting and the parent of origin effect.

Placental Mammals and Marsupials are the only class of life on this planet that cannot reproduce asexually. Insects, Reptiles, Amphibians, and etc. all have some member of their class that can reproduce on their own without fertilization. What it is that makes Mammals and Marsupials unique in this aspect, is a fascinating area of epigenetics known as genomic imprinting.

Descriptively, genomic imprinting is when certain regions on chromosomes contain methylation patterns that did not arise from any process of development. These methylation patterns are present before the fertilization event, on the chromosomes of the gametes.
These unique methylation patterns convey information about which parent (Paternal or Maternal) the chromosomes originated from. Hence the commonly used phrase “parent of origin effect”. In mammals this phenomenon is localized to a few hundred or so genes. These genomic imprints are not removed at any point as egg and sperm fuse to form a zygote or as the zygote undergoes the incredibly long and difficult process of dividing and differentiating into trillions of cells and various different cell types.

Theoretically genomic imprinting allows for more precision in gene expression. From a cost benefit perspective, it makes sense as to why this process occurs in only a hundred or so genes. Diploid chromosomes provide us with a backup system: if one gene becomes defective the other spare copy can still perform the necessary function (for example, women tend not to display Duchenne muscular dystrophy even if one of their dystrophin genes is defective because they inherit two copies of the gene, one on each X chromosome). In imprinting, mammals are sacrificing this backup system in exchange for more precise signaling. One could suggest that this precise signaling is needed for the features that make mammals unique: their neocortex and the complex metabolism required to fuel it.

This is further illustrated by diseases and disorders associated with imprinting errors: in both Prader Willi Syndrome and Angelman Syndrome patients have cognitive and metabolic problems. They do not develop any major pathologies of any other organ system. Angelman and Prader Willi diagnosed patients have phenotypically normal skin, for example.

It is also worth pointing out that one of the reasons why problems with genomic imprinting and other “epigenetic diseases (including long non-coding RNAs) ” are so adamantly manifested in neurological diseases such as: Prader Willi Syndrome, Angelman Syndrome, Rhett Syndrome, friedreich’s ataxia, Fragile X syndrome, Alzheimers, Rubinstein-Taybi Syndrome, frontotemporal lobar degeneration, depression, and schizophrenia. Is that unlike all other major organ systems, the development of the central nervous system takes an exceptionally long period of time. The consequences of this is that while most of the epigenetic structure of other organs such as the bones and skeletal muscles is established and kept relatively consistent shortly after development, the brain needs to utilize these epigenomic mechanism extensively and over a much longer period of time than its other mesodermal and ectodermal counterparts. This process is heavily reliant upon fine tuning and long term action of genomic imprinting and epigenetic modifications.

The actual mechanism that explains genomic imprinting is poorly defined and illustrated. There is a consensus that during the process of gametogenesis the methylation patterns indicating which parent a chromosome originated from is removed and replaced with either a Maternal or Paternal methylation pattern. We do not yet have a complete mechanistic framework that explains this process, or more specifically, an explanation of how these highly resistant methylation patterns are removed and then replaced in gametogenesis.

Doctors Shinya Yamanaka and John Gurdon won a Nobel prize for their work in synthetically removing epigenetic modifications to cells to induce them back to a pluripotent stem cell state (iPS cells). Understanding how these imprints are put on and removed will provide an essential step in bridging the gap between biological research and clinical medicine, as well as other applications.