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The role of genomic imprinting in biology and disease: an expanding view

Key Points

  • Genomic imprinting — an epigenetic phenomenon that results in monoallelic expression according to parental origin — was recognized in mammals around 30 years ago from embryological and genetic studies.

  • Imprinted genes are known to have major effects on prenatal development and placental biology. More recently, they have been shown to exert important effects on postnatal development, growth and survival, as well as on adult phenotypes.

  • Imprinted genes are emerging as key regulators of metabolic processes in both infants and adults. They can influence maintenance of body temperature, food intake and adiposity by acting on multiple tissues and pathways.

  • Many imprinted genes are expressed in the brain and affect diverse aspects of behaviour from birth onwards, from infant feeding to sleep and adult social behaviour.

  • Investigations of mouse mutants have been important in unravelling the roles of imprinted genes and for elucidating some of the pathophysiological mechanisms involved in human imprinted syndromes.

  • Disrupted expression of imprinted genes is an important cause of human disease. In addition to known imprinted syndromes, there is increasing evidence that altered expression of imprinted genes is a contributory factor in a wide range of common diseases, such as intrauterine growth restriction, obesity, diabetes mellitus, psychiatric disorders and cancer.


Genomic imprinting is an epigenetic phenomenon that results in monoallelic gene expression according to parental origin. It has long been established that imprinted genes have major effects on development and placental biology before birth. More recently, it has become evident that imprinted genes also have important roles after birth. In this Review, I bring together studies of the effects of imprinted genes from the prenatal period onwards. Recent work on postnatal stages shows that imprinted genes influence an extraordinarily wide-ranging array of biological processes, the effects of which extend into adulthood, and play important parts in common diseases that range from obesity to psychiatric disorders.

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Figure 1: Representative mouse imprinted gene clusters.
Figure 2: Imprinted genes affect metabolism.
Figure 3: Imprinted genes regulate behaviours.


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The author thanks B. Cattanach, G. Moore, A. Plagge and V. Tucci for discussions and comments. Given the broad scope of this Review, the author apologizes to colleagues whose work was not cited owing to space limitations.

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Correspondence to Jo Peters.

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Pertaining to the pronucleus (that is, the haploid nucleus from a male or female gamete).

Gene dosage

The number of expressed copies of a gene in a cell.

CCCTC-binding factor

(CTCF). A highly conserved zinc-finger protein that influences chromatin organization and architecture; it is implicated in diverse regulatory functions, including transcriptional activation, repression and insulation.


Pertaining to heritable but potentially reversible changes in gene expression that are caused by mechanisms other than changes in the underlying DNA sequence.

Uniparental disomy

(UPD). A cellular or organismal phenomenon in which both chromosome homologues are derived from one parent and none from the other parent. It can be the result of fertilization that involves a disomic gamete and a gamete that is nullisomic for the homologue.

Metabolic syndrome

A group of metabolic conditions that occur together and that increase the risk of developing cardiovascular disease, stroke and diabetes.

Metabolic programming

The response to adverse conditions during early development that results in resetting of metabolic responses and predisposition to metabolic syndrome in adulthood.

Rapid eye movement

(REM). A phase of sleep that is characterized by rapid and random movement of the eyes, low muscle tone and a rapid low-voltage electroencephalogram. It is associated with dreaming, and many brain areas are active during REM sleep.


(NREM). A phase of sleep that is characterized by slow or no eye movement. Non-REM sleep is divided into three stages, which have distinct brain wave patterns, and deep or slow wave sleep occurs in stage three. There is relatively little dreaming in non-REM sleep.

Fear conditioning

A behavioural paradigm in which organisms learn to predict adverse events.

Facial barbering

The trimming and plucking of the whiskers and fur of one mouse by another.

Tube test

A test of social dominance in which two unfamiliar mice are placed head first at opposite ends of a tube. The socially dominant mouse remains in the tube, whereas the more submissive mouse retreats from the tube.

Complete hydatidiform mole

A conceptus that lacks a set of normal maternal chromosomes and that forms a tumour-like mass. Known causes include a failure to set imprints in the female germ line and the occurrence of a conceptus that has both sets of chromosomes of paternal origin.


Mutations that result in heritable changes in gene expression that are caused by mechanisms other than changes in the underlying DNA sequence.


A genetic element that can be transposed to a new site in the genome by forming an RNA transcript that can be copied to DNA using reverse transcriptase, which can then be integrated into the genome.

Reciprocal hybrids

F1 hybrid mice produced from reciprocal crosses between two mouse strains or between Mus musculus subspecies.

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Peters, J. The role of genomic imprinting in biology and disease: an expanding view. Nat Rev Genet 15, 517–530 (2014).

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