You inherit two copies of almost every gene, one from each parent, and usually both can work. For a small group of genes, though, the body switches one parent’s copy off and relies only on the other, depending purely on which parent it came from.1PubMed. Mechanisms and evolution of genomic imprinting in plants The reason may be less about cooperation than about mothers’ and fathers’ genes pulling in different directions over how a pregnancy is fed.2Santa Fe Institute. Maternal vs. Paternal Imprinting: How Parent-of-Origin Works A single missing copy can therefore cause very different conditions depending on whether it was mom’s or dad’s.
What It Means When a Gene Is Imprinted
An imprinted gene is one where the copy used depends on whether it came from the mother or the father.3PubMed. Genomic imprinting in plants: what makes the functions of paternal and maternal genes different in endosperm formation? The two copies can be identical in their DNA spelling and still behave differently.
The two sets of chromosomes are not interchangeable. Mouse embryos built with two mothers’ chromosome sets, or two fathers’ sets, failed to develop to birth.4PubMed Central. The discovery and importance of genomic imprinting
A silenced copy is not a broken gene. Its DNA letters are intact, and chemical tags simply keep it off. That makes imprinting different from a recessive gene, where a second working copy hides the problem: here the backup copy exists but is switched off. With only one copy working, a harmful change in that active copy has nothing to cover for it, so imprinted genes are more vulnerable than most.
The naming can confuse. “Maternally imprinted” usually means the mother’s copy is the one turned off, so a maternally imprinted gene is “paternally expressed,” and the father’s copy does the work. In general, genes that work from dad’s copy tend to boost growth of the fetus and placenta, while genes working from mom’s copy tend to hold growth back.5PubMed. Imprinted genes and the epigenetic regulation of placental phenotype
Only a small minority of genes are imprinted, and most use both copies. Imprinted genes often sit together in clusters on a chromosome, and many are active in the placenta and the brain, where their effects show most.
How the Body Marks Which Parent a Gene Came From
Parent-of-origin tags are added while eggs and sperm are being made.6Cell Research. Genomic imprinting in mammals: its life cycle, molecular mechanisms and reprogramming An epigenetic tag is a chemical group that sits on DNA or its packaging without changing the genetic letters. Cells copy the tags when they divide, so the instruction persists. Unlike the DNA spelling, tags can be added, lost, or reset. They pass to the embryo at fertilization and are kept through development and adult life.7Cell Research. Genomic imprinting in mammals: its life cycle, molecular mechanisms and reprogramming That is notable, because right after fertilization the embryo wipes most chemical tags across its DNA, and imprinted genes escape that wipe.8PubMed Central. Genomic imprinting: employing and avoiding epigenetic processes Later, in a person’s own future egg or sperm cells, the old marks are erased and new ones matching that person’s sex are set.9Cell Research. Genomic imprinting in mammals: its life cycle, molecular mechanisms and reprogramming
The reset is needed because a person carries one copy from each parent, and each must be labelled by the person’s own sex for the next generation. A woman’s eggs carry maternal marks even on the copy she inherited from her father, so the old label cannot just be passed along. A grandmother’s gene passed through a son becomes a “father’s copy” in the grandchild. If the erasure or rewriting fails, a child can inherit a gene with the wrong label, which is one route to an imprinting disorder.
Each imprinted cluster has a control region whose chemical tags steer the genes around it, and those patterns persist in most body cells.10PubMed Central. The Role of Long Non-coding RNAs in Human Imprinting Disorders: Prospective Therapeutic Targets Many clusters also produce long RNA molecules that don’t make proteins but silence neighbouring genes on the same chromosome.11PubMed Central. The Role of Long Non-coding RNAs in Human Imprinting Disorders: Prospective Therapeutic Targets Some genes use a second kind of mark, a tag on the protein packaging around DNA. It is inherited from the egg and kept mainly in the early embryo and placenta.12PubMed. Noncanonical imprinting: intergenerational epigenetic inheritance mediated by Polycomb complexes Because it works even when the usual DNA tags are missing, it gives those genes a backup route to parent-specific control.13PubMed Central. Maternal H3K27me3-dependent autosomal and X-chromosome imprinting
Why Evolution Favors Parent-Specific Genes
The dominant explanation since 1991 is the parental conflict, or kinship, theory.14Santa Fe Institute. Maternal vs. Paternal Imprinting: How Parent-of-Origin Works A father’s gene in one baby may not be shared with that mother’s other babies, so it gains by grabbing more of her resources.15PubMed. The conflict theory of genomic imprinting: how much can be explained? A mother’s genes are in all her children, so they gain by sparing her resources for future pregnancies.16Santa Fe Institute. Maternal vs. Paternal Imprinting: How Parent-of-Origin Works Models show this tug-of-war can produce strongly one-sided gene use, provided mothers sometimes have offspring with more than one father.17Population Ecology. Conflict theory of genomic imprinting in mammals If a mother always had children with the same father, his genes and hers would share the same interest in all the babies, and the pull would weaken.
The evidence fits: growth-boosting genes tend to work from dad’s copy and growth-limiting ones from mom’s, as the theory predicts.18PubMed. Imprinted genes and the epigenetic regulation of placental phenotype Flowering plants evolved imprinting independently, and there it acts in the seed tissue that feeds the embryo.19PubMed. Mechanisms and evolution of genomic imprinting in plants The theory explains prenatal growth genes well, but the roles of imprinted genes after birth are less clear.
Which Animals and Plants Have Imprinting
Egg-laying mammals like the platypus show no sign of imprinting, despite a short-lived placenta.20PubMed Central. The origin and evolution of genomic imprinting and viviparity in mammals Marsupials and placental mammals, however, share imprinted regions.21PubMed Central. The origin and evolution of genomic imprinting and viviparity in mammals Imprinting likely arose with live birth in a shared ancestor at least 160 million years ago.22Heredity. Post-natal imprinting: evidence from marsupials Egg-laying mammals do not nourish their young through a long-lived placenta, so the resource tug-of-war would be weaker, which fits imprinting being linked to how much a mother supplies before birth.
Angelman and Prader-Willi Syndromes
A region on chromosome 15 holds genes imprinted in opposite directions.23Nature Education. Imprinting and Genetic Disease: Angelman, Prader-Willi and Beckwith-Weidemann Syndromes Losing a working copy from dad causes Prader-Willi syndrome, while losing a working copy of the UBE3A gene from mom causes Angelman syndrome.24PubMed. Mechanisms of imprinting of the Prader-Willi/Angelman region In each case the other parent’s copy is already switched off and cannot fill in.25Nature Education. Imprinting and Genetic Disease: Angelman, Prader-Willi and Beckwith-Weidemann Syndromes
The two look different. Prader-Willi typically brings weak muscle tone in infancy, then constant hunger later. Angelman typically brings severe speech delay, balance problems, seizures and a happy demeanour. Both involve developmental delay, which is why testing is needed to tell them apart.
About 70% of Angelman cases come from a missing piece of mom’s chromosome 15.26Nature Education. Imprinting and Genetic Disease: Angelman, Prader-Willi and Beckwith-Weidemann Syndromes The other 30% come from other genetic changes, such as both copies coming from dad or a faulty mark.27Nature Education. Imprinting and Genetic Disease: Angelman, Prader-Willi and Beckwith-Weidemann Syndromes Getting both chromosome 15s from a single parent can go either way. Two dad copies leave no working mom UBE3A, giving Angelman. Two mom copies leave no working dad genes, giving Prader-Willi.
A common first test checks the methylation pattern in the chromosome 15 region, which can show that the maternal or paternal pattern is missing. Other tests then look for a missing piece of chromosome, both chromosomes from one parent, or a change in the UBE3A gene itself. Knowing which route applies matters because the chance of it happening again differs between types. If your child has a diagnosis, ask the genetics team whether your child’s type carries a recurrence risk for future pregnancies.
Growth Syndromes and Cancer
Beckwith-Wiedemann syndrome causes overgrowth and Silver-Russell syndrome causes growth restriction.28PubMed. Beckwith-Wiedemann and Silver-Russell syndromes: opposite developmental imbalances in imprinted regulators of placental function and embryonic growth Most cases come from opposite errors in the same imprinted region on chromosome 11.29PubMed. Beckwith-Wiedemann and Silver-Russell syndromes: opposite developmental imbalances in imprinted regulators of placental function and embryonic growth A baby with Beckwith-Wiedemann may be born larger than expected, and some have an enlarged tongue or organs. A baby with Silver-Russell is typically small before birth and tends to stay small afterwards.
The same region drives some childhood tumours as well as overgrowth, which is why children with Beckwith-Wiedemann usually get regular tumour screening. Ask the care team about the recommended ultrasound schedule.
Loss of imprinting means a normally silent copy switches on, so both copies work.30OBM Genetics. Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment The growth gene IGF2 loses imprinting in most Wilms’ tumours, a childhood kidney cancer.31PubMed. Loss of imprinting of IGF2 is linked to reduced expression and abnormal methylation of H19 in Wilms’ tumour When this happens, IGF2 output roughly doubles.32PubMed Central. Loss of Imprinting of IGF2 as an Epigenetic Marker for the Risk of Human Cancer Several other cancer types overproduce IGF2, often through this same loss of imprinting.33OBM Genetics. Insulin-Like Growth Factor 2 in Physiology, Cancer, and Cancer Treatment
Can IVF or a Parent’s Diet Change Imprinting
Hormone stimulation, sperm injection and embryo culture happen exactly when imprints are being set or protected.34PubMed Central. The impact of assisted reproductive technologies on genomic imprinting and imprinting disorders These steps may contribute to errors in imprinting control regions.35PubMed Central. Imprinting Disorders and Epigenetic Alterations in Children Conceived by Assisted Reproductive Technologies: Mechanisms, Clinical Outcomes, and Prenatal Diagnosis Frozen embryo transfer and embryo genetic testing are also under study for effects on these marks.36PubMed. Genetic and epigenetic risks of assisted reproduction
Researchers look at IVF because eggs complete their imprints late in development, so hormone stimulation touches that window, and embryo culture happens just after fertilization, when imprints must be protected. The overlap is not proof that the steps are harmful.
Imprinting disorders remain rare even in children conceived by IVF, and most IVF children are healthy. Some risk may come from underlying infertility, not only the procedures. Prenatal testing can check for some imprinting disorders. If you’re considering IVF, ask your clinic what current data show about imprinting disorders.
Diet, hormones and toxins can affect imprinting while eggs and sperm form.37Learn.Genetics. Genomic Imprinting Both mothers’ and fathers’ nutrition may shape offspring imprinting,38PubMed Central. Perinatal nutrition as a key regulator of genomic imprinting: a new paradigm for maternal-child health so a father’s health before conception may matter too.
Switching a Silent Copy Back On
In Angelman, dad’s UBE3A copy is healthy but kept silent by a long RNA.39PubMed Central. UBE3A reinstatement as a disease‐modifying therapy for Angelman syndrome In nerve cells, that RNA runs in the opposite direction across dad’s gene and blocks it from being read. So a healthy paternal copy is present but does nothing in the brain.
An antisense oligonucleotide (ASO) is a short engineered strand that latches onto that RNA and has it destroyed, which can unsilence dad’s copy.40PubMed Central. UBE3A reinstatement as a disease‐modifying therapy for Angelman syndrome It is made to match the letters of the long RNA, so it binds only to that target. Once bound, the cell’s own machinery recognises the pair and breaks the RNA down. With the blocker gone, dad’s UBE3A copy can be read and the cell makes the missing protein. ASOs aimed at the start of that RNA restored UBE3A in nerve cells grown from people with Angelman.41PubMed. An ASO therapy for Angelman syndrome that targets an evolutionarily conserved region at the start of the UBE3A-AS transcript They are favoured because they allow better control over dose and where the drug goes than virus-based approaches.42PubMed Central. UBE3A reinstatement as a disease‐modifying therapy for Angelman syndrome Results so far are early, and Angelman organisations are a good place to ask about clinical trials.