Most of us inherit two copies of nearly every gene—one from our mother and one from our father. Usually, cells treat those copies as functionally equivalent. But a small and important group of genes works differently: which parent a gene came from can determine whether it is active.
This phenomenon is called genomic imprinting. It is an epigenetic process in which chemical marks placed on DNA or its associated proteins distinguish a gene inherited from the mother from the corresponding gene inherited from the father. Those marks can cause one parental copy to be active while the other is largely silent.
Genomic imprinting helps regulate growth, development, metabolism, and other biological processes. It also explains why certain genetic disorders can depend not only on which gene variant a person inherits, but on whether that variant came from the mother or the father.
What makes an imprinted gene different?
For most genes, inheriting one altered copy does not depend on its parental origin in the way an imprinted gene does. Both copies may be expressed, meaning that the cell uses both copies to make RNA or protein.
With an imprinted gene, however, one copy is preferentially expressed according to its parent of origin. The copy inherited from one parent may be active, while the copy inherited from the other is silenced or expressed at a much lower level.
This does not mean that the parent’s DNA sequence is fundamentally different. The maternal and paternal copies can have the same underlying sequence but carry different epigenetic marks.
Epigenetics refers to changes that influence how genes are used without changing the DNA sequence itself. In genomic imprinting, these marks act as molecular instructions about parental origin. One of the most important marks is DNA methylation, in which small chemical groups called methyl groups are attached to particular DNA bases. Other changes involving DNA-associated proteins and regulatory regions also contribute to imprinting.
The result is a kind of parent-specific gene regulation: the cell can distinguish the maternal copy from the paternal copy and use them differently.
How genomic imprinting is established
Imprinting marks are established in the cells that give rise to eggs and sperm. During the formation of eggs, particular regions receive maternal imprinting patterns; during sperm formation, corresponding regions can receive paternal patterns.
After fertilization, the embryo therefore contains a genome carrying information about parental origin. Although the early embryo undergoes extensive epigenetic reprogramming, certain imprinting marks are protected and maintained.
As development proceeds, these marks help determine which parental copy of an imprinted gene is expressed in particular tissues.
Importantly, imprinting is not simply a permanent label attached to an individual’s DNA from birth. Imprinting marks must be reset during the formation of eggs and sperm so that they reflect the sex of the individual producing the gamete. A person carries inherited maternal and paternal imprinting patterns, but when that person’s germ cells develop, the relevant imprints are erased and re-established according to whether those cells will produce eggs or sperm.
This resetting is essential for imprinting to function correctly across generations.
Why does parent of origin matter?
The practical consequence is easiest to see when a person inherits a disease-causing variant in an imprinted gene.
Suppose a particular gene is normally expressed only from the paternal copy, while the maternal copy is normally silenced. If a child inherits a harmful variant in the paternal copy, the child may have little or no functional gene product because the normally silent maternal copy cannot compensate.
If the same variant is inherited from the mother, the paternal copy may remain functional, so the child could be unaffected or have a substantially different outcome.
The reverse situation can occur for a gene normally expressed from the maternal copy.
Thus, the same DNA variant can have different consequences depending on which parent transmitted it. This is one of the clearest examples of why understanding a genetic disorder sometimes requires more than identifying the DNA sequence itself.
Imprinting and human disease
Disruptions of imprinted genes or their regulatory regions are associated with several human disorders. Two of the best-known examples involve a region of chromosome 15 and illustrate the principle particularly clearly.
Prader-Willi syndrome can occur when certain genes that are normally expressed from the paternal chromosome 15 are missing or otherwise disrupted. The corresponding maternal copies are normally imprinted and therefore do not provide the expected expression from that region.
Angelman syndrome involves a different pattern. In certain forms of the disorder, loss of function of the maternally expressed UBE3A gene in neurons contributes to the condition. The paternal copy is normally silenced in those neurons, so it cannot simply substitute for the missing maternal activity.
These disorders demonstrate that genetic information is not always interchangeable between the two copies of a chromosome. The same region can have different functional consequences depending on its parental origin.
Imprinting abnormalities can also arise through mechanisms other than a conventional DNA sequence mutation. A person may inherit the appropriate DNA sequence but have an abnormal imprinting pattern, or may receive an unusual combination of parental chromosomes.
Uniparental disomy: when both copies come from one parent
A related concept is uniparental disomy, or UPD. Normally, a person receives one copy of each chromosome from each parent. In uniparental disomy, both copies of a chromosome—or part of a chromosome—come from the same parent.
UPD can matter because it changes the normal balance of maternal and paternal imprinted genes.
For example, if a child receives two copies of a chromosome from the mother and none from the father, genes that normally require paternal expression may be missing their expected active copy. Conversely, two paternal copies can produce an excess of paternal expression and a lack of maternal expression.
UPD can therefore cause disease even when the chromosome itself does not carry a conventional disease-causing mutation.
Imprinting is different from ordinary genetic inheritance
It is useful to separate three concepts that can otherwise become confusing.
A genetic mutation changes the DNA sequence. The change may alter the function of a gene.
An epigenetic change alters how genetic information is regulated without necessarily changing the DNA sequence.
Genomic imprinting is a specialized form of epigenetic regulation in which gene activity depends on parental origin.
These mechanisms can interact. A disease-causing DNA variant in an imprinted gene may have consequences only when inherited from one particular parent. Alternatively, an abnormal imprinting pattern can disrupt gene activity without a mutation in the gene’s protein-coding sequence.
Why imprinted genes are biologically important
Imprinted genes are especially prominent in processes involving growth and development. Many influence fetal growth, placental function, metabolism, and the regulation of cell growth.
Researchers have proposed several evolutionary explanations for why parental genomes might regulate some genes differently. One influential idea involves differences in the evolutionary interests of maternal and paternal genomes over the allocation of resources to offspring. This framework helps explain why many imprinted genes are involved in growth and resource use, although it does not by itself explain every feature of imprinting.
Imprinting also highlights an important principle of developmental biology: having two copies of a gene does not always mean having two equivalent sources of gene activity.
What happens when imprinting goes wrong?
Imprinting can be disrupted at several levels. The DNA sequence of an imprinted gene can be altered. A chromosome or chromosome segment can be inherited from only one parent. Or the epigenetic marks that normally distinguish maternal and paternal copies can be incorrectly established, maintained, or interpreted.
Because imprinting regulates gene activity rather than simply changing the DNA sequence, laboratory diagnosis may require methods that examine both genetic sequence and epigenetic or chromosomal patterns. The appropriate testing depends on the disorder and the suspected mechanism.
The effects can also vary by tissue. An imprinting pattern that is important in one tissue may differ from the pattern in another. A well-known example is the paternal silencing of UBE3A in neurons, which helps explain why loss of the maternal copy has particular neurological consequences in Angelman syndrome.
Why imprinting matters for genetic counseling
Genomic imprinting can change the way a family’s risk is interpreted.
For many inherited conditions, identifying which parent carries a variant is less important than identifying the variant itself. With an imprinted gene, parental origin may be central to predicting whether a variant is likely to cause disease.
This can make family histories more informative. Two relatives may carry related genetic changes yet have different clinical outcomes because the changes were inherited through different parental lines or because their imprinting status differs.
For families affected by an imprinting disorder, genetic counseling can therefore involve questions about the exact molecular mechanism, parental origin, chromosome inheritance, and the possibility of recurrence in future pregnancies.
The larger lesson of genomic imprinting
Genomic imprinting challenges a simple view of heredity in which a gene is merely a piece of DNA passed from one generation to the next. The DNA sequence is essential, but cells also interpret that sequence in a regulatory context.
For a relatively small set of genes, that context includes a record of which parent supplied the copy. Epigenetic marks established during the formation of eggs and sperm preserve that distinction, allowing maternal and paternal copies of the same gene to have different roles.
That is why, in genomic imprinting, knowing what genetic information a person inherited is sometimes not enough. To understand its biological effect, you may also need to know where it came from.
