Our bodies are built from intricate biological instructions encoded in our genes. Each individual inherits two copies of every gene, one from each parent. For most genes, both copies are active and contribute to our traits. However, some genes present a unique exception to this inheritance pattern. These are known as imprinted genes.
The Unique Nature of Imprinted Genes
Imprinted genes are distinct because their expression depends on which parent they came from. Unlike most genes where both maternal and paternal copies are active, only one copy of an imprinted gene is expressed, while the other is silenced. This silencing is not due to a mutation or defect in the DNA sequence, but is a normal, regulated process. This parent-of-origin specific expression differs from typical inheritance patterns. For example, if a child inherits genes for blood group A from one parent and blood group B from the other, both are expressed. Imprinted genes defy this, with only one parental allele being functional.
The Mechanisms Behind Imprinting
The specific expression of imprinted genes is achieved through epigenetic modifications, which alter gene activity without changing the underlying DNA sequence. DNA methylation is a primary mechanism involved. During the formation of sperm and egg cells, specific DNA regions are “marked” by adding methyl groups to cytosine bases. This methylation often silences the gene on that parental chromosome.
Other epigenetic marks, such as histone modifications, also regulate imprinted gene expression. Histones are proteins around which DNA is wound; chemical changes to these histones can affect how tightly DNA is packed, influencing gene accessibility and expression. These epigenetic tags are established at specific regions called imprinting control regions (ICRs), which are important for proper imprinted gene regulation.
How Imprinted Genes Are Passed Down
The inheritance pattern of imprinted genes is unique because the epigenetic “imprint” is reset in the offspring’s germline. This means a gene’s imprinting status is reprogrammed based on the sex of the individual producing gametes. For instance, a male’s sperm will carry a paternal imprint for all imprinted genes, even if he inherited a maternally expressed copy. Conversely, a female will establish maternal imprints in her eggs.
This reprogramming ensures correct parent-of-origin specific expression across generations. For example, if a gene is expressed from the mother’s copy, a female offspring will pass on a maternally imprinted (expressed) copy. A male offspring inheriting that same gene will reset its imprint, passing on a paternally imprinted (silenced) copy. This resetting mechanism is important for proper development.
The Role of Imprinted Genes in Health and Disease
Imprinted genes play a significant role in normal fetal development, growth, and brain function. For example, paternally expressed imprinted genes often promote offspring growth, while maternally expressed ones tend to limit it, suggesting a “parental battle” over resource allocation during pregnancy. This balance highlights their importance.
When imprinting goes awry, such as through errors in methylation patterns, deletions of imprinted regions, or uniparental disomy (inheriting two copies of a chromosome from one parent), it can lead to various human disorders. Prader-Willi syndrome and Angelman syndrome are two well-known examples linked to imprinting defects on chromosome 15q11-q13. Prader-Willi syndrome results from the absence of paternally expressed genes in this region, often due to a deletion on the paternal chromosome 15 or inheriting two maternal copies. Affected individuals often experience weak muscles in infancy, followed by insatiable hunger, obesity, and intellectual impairment.
Conversely, Angelman syndrome arises from the loss of function of the maternally expressed UBE3A gene within the same chromosome 15 region. This can occur if the maternal copy of the gene is deleted or not working properly, or if two paternal copies of chromosome 15 are inherited. Individuals with Angelman syndrome often exhibit developmental delays, severe speech impairment, and characteristic movement or balance disorders. These distinct conditions, resulting from issues with different parental copies of genes in the same chromosomal region, highlight the precise regulation required for imprinted genes and their impact on human health.