From the Guidelines
Genetic imprinting is a biological process where certain genes are expressed differently depending on whether they were inherited from the mother or father, and it is crucial for normal development, with disruptions leading to various disorders such as Prader-Willi syndrome and Angelman syndrome. This phenomenon occurs because one parent's copy of the gene is silenced through epigenetic modifications, primarily DNA methylation, while the other parent's copy remains active 1. For instance, in the context of Prader-Willi syndrome, the absence of the paternally inherited contribution of the PWS region of chromosome 15 leads to a lack of gene products, causing the findings of PWS, whereas the absence of the maternally inherited contribution of this region causes Angelman syndrome 1.
The mechanisms underlying genetic imprinting involve a change to the genomic structure that affects regulation of expression, rather than a change in the sequence of the DNA itself 1. Key to this process is the "imprinting center," a short sequence of DNA that controls switching and maintenance of the imprinting pattern, which is critical for reactivating silenced genes inherited from the mother when passed to offspring 1. Disruptions in imprinting can occur through various mechanisms, including microdeletions, maternal uniparental disomy, imprinting errors, and balanced translocations involving the chromosome with the imprinted region 1.
Understanding genetic imprinting is essential for diagnosing and managing disorders related to imprinting defects, as the recurrence risk can vary significantly depending on the underlying mechanism, with imprinting errors and certain balanced translocations potentially leading to a higher risk of recurrence in subsequent pregnancies 1. The evolutionary purpose of imprinting is thought to relate to the balance of resource allocation during fetal development, reflecting the potentially conflicting interests of maternal and paternal genes regarding maternal resource investment in offspring.
Some of the key disorders associated with genetic imprinting include:
- Prader-Willi syndrome
- Angelman syndrome
- Beckwith-Wiedemann syndrome These disorders highlight the importance of genetic imprinting in normal development and the significant consequences of disruptions to this process.
From the Research
Definition of Genetic Imprinting
- Genetic imprinting is defined as a reversible, differential marking of genes or chromosomes that is determined by the sex of the parent from whom the genetic material is inherited 2.
- It is a process where one of the two alleles of a gene is silenced or "stamped" based on its parental origin, resulting in the expression of only one allele 3.
Mechanisms of Genetic Imprinting
- The mechanisms of genetic imprinting involve epigenetic modifications, such as DNA methylation, which are erased and then reset during the creation of eggs and sperm 3.
- The repressed allele is methylated, while the active allele is unmethylated 3.
Effects of Genetic Imprinting
- Genetic imprinting affects several dozen mammalian genes and results in the expression of those genes from only one of the two parental chromosomes 4.
- Imprinting is thought to influence the transfer of nutrients to the fetus and the newborn from the mother, and aberrant imprinting can disturb development and cause various disease syndromes 4.
- Genetic imprinting plays a critical role in fetal growth and behavioral development, and is regulated by DNA methylation and chromatin structure 5.
Examples of Genetic Imprinting
- Examples of genetic imprinting include Prader-Willi syndrome and Angelman syndrome, which can be caused by imprinting or other errors involving genes on the long arm of chromosome 15 3.
- Genetic imprinting is also involved in the development of other diseases, such as cancer and behavioral disorders, and can be influenced by environmental factors 5.