Most of our genes come in two working copies, one inherited from each parent, and both copies are usually active at the same time. A small number of genes do not follow that rule. For these genes, the body normally keeps only one parent's copy switched on and silences the other, based entirely on which parent it came from. This phenomenon is called genomic imprinting.
Imprinting is set during the formation of egg and sperm cells, through a chemical marking process called methylation, which attaches small molecules to specific stretches of DNA. These marks do not change the DNA sequence itself. They act more like a label that tells a cell whether a particular copy of a gene came from the mother or the father, and whether that copy should be active. Only a small percentage of human genes are imprinted this way, and imprinted genes tend to cluster together in specific chromosome regions rather than being spread evenly across the genome.
Because only one parental copy is normally active for an imprinted gene, these genes are unusually vulnerable. If the single active copy is lost, through a deletion, a gene variant, or an unusual inheritance pattern called uniparental disomy, a person can end up with no working copy of that gene at all, even though the silenced copy from the other parent is still physically present. Uniparental disomy happens when someone inherits two copies of a chromosome, or part of one, from a single parent instead of one copy from each parent. For most genes this causes no problem, since most genes are not imprinted and it does not matter which parent a working copy came from. For an imprinted gene, though, uniparental disomy can leave a person without any active copy, because the two copies they have are both the type that is normally silenced.
A real example: Angelman syndrome
One of the clearest illustrations of imprinting involves a region on the long arm of chromosome 15, around position 15q11 to 15q13. A gene in this region, UBE3A, is imprinted specifically in nerve cells of the brain and spinal cord. In most tissues of the body, both copies of UBE3A are active, but in these nervous system cells, only the copy inherited from the mother is normally switched on. The father's copy is silenced there.
When the maternal copy of UBE3A is lost or disrupted, there is no active copy left in the brain, because the paternal copy was never turned on in those cells to begin with. This loss of maternal UBE3A activity causes Angelman syndrome, a condition marked by developmental delay, intellectual disability, limited speech, and problems with movement and balance. Most cases happen when a segment of the maternal chromosome 15 containing the gene is deleted, and a smaller share result from a variant in the maternal copy of the gene itself or from paternal uniparental disomy, where a person inherits two paternal copies of chromosome 15 and no maternal one. Most cases are not inherited from a parent who carries the same condition. They arise as random events during egg or sperm formation or in very early development, so a family history of Angelman syndrome is uncommon.
Prader-Willi syndrome is often discussed alongside Angelman syndrome because it involves the same stretch of chromosome 15, but the parent of origin is reversed. Prader-Willi syndrome results from the loss of paternally active genes in that region, commonly through a deletion on the father's chromosome 15 or through maternal uniparental disomy. Its features, including weak muscle tone in infancy and later overeating with obesity, are quite different from those of Angelman syndrome, which underscores how much the parent of origin matters for an imprinted region. Both conditions show the same underlying principle from opposite directions: losing the one active parental copy of an imprinted gene, rather than simply having too little DNA, is what drives the clinical picture.
Why this matters for families
Genomic imprinting helps explain why two genetic changes that look similar on paper, such as a deletion on the same stretch of chromosome 15, can produce very different conditions depending on whether the deleted copy came from the mother or the father. It also explains why a de novo variant or a chromosomal change that would be harmless for most genes can matter a great deal when it lands on an imprinted one. This is different from the more familiar inheritance patterns described for autosomal dominant, autosomal recessive, and X-linked conditions, where both parents' copies are typically treated the same way by the body.
In practice, a family facing a diagnosis linked to an imprinted region will usually be referred for detailed testing that can identify the specific mechanism involved, since a deletion, a point variant, and uniparental disomy can carry different implications for recurrence risk in future pregnancies. A genetic counselor can walk through what the specific result means for that family.
This page is educational and not a substitute for a clinical evaluation. A diagnosis involving genomic imprinting should be confirmed and interpreted by a qualified clinician or genetic counselor, who can also review options for testing and family planning.