Genomic imprinting represents an exception to typical inheritance patterns, where the origin of a gene, whether from the mother or the father, dictates its activity. This process ensures that some genes are expressed from only one parent’s inherited copy, while the other copy remains silent. It highlights a layer of genetic regulation beyond the DNA sequence itself, influencing how our inherited traits manifest.
What is Genomic Imprinting?
Genomic imprinting is a biological process where certain genes are expressed in a parent-of-origin-specific manner. This means only the copy inherited from either the mother or the father is active, while the other copy is silenced. This differs from standard Mendelian inheritance, where both copies of a gene, one from each parent, are typically expressed. The silencing of one gene copy happens without altering the underlying DNA sequence itself.
Instead, gene expression is controlled by chemical modifications, referred to as epigenetic tags. These tags are added to the DNA during the formation of egg or sperm cells and are maintained throughout an individual’s life in their somatic cells.
The Parental Distinction: Maternal Versus Paternal Imprinting
The distinction between maternal and paternal imprinting lies in which parent’s gene copy is actively expressed. In maternal imprinting, the gene inherited from the mother is expressed, and the paternal copy is silenced. Conversely, paternal imprinting occurs when the gene inherited from the father is expressed, and the maternal copy is silenced.
For example, the IGF2 gene, which codes for insulin-like growth factor-2, is paternally expressed. In humans, the IGF2 allele inherited from the father is expressed, while the mother’s inherited copy is not. In contrast, the H19 gene, which produces a non-coding RNA, is an example of maternal expression; the copy from the mother is active and the paternal copy is silenced.
How Imprinting Works
The molecular mechanisms underlying genomic imprinting primarily involve epigenetic modifications, which alter gene expression without changing the DNA sequence. A key mechanism is DNA methylation, where a methyl group is added to cytosine bases within specific DNA regions, often found in CpG dinucleotides. This methylation leads to gene silencing by preventing proteins that activate gene expression from binding to the DNA.
These epigenetic marks are established in the germline cells (sperm or egg) of the parents and are maintained as the organism develops. In addition to DNA methylation, other factors contribute to imprinting, including histone modifications. Histones are proteins around which DNA is wrapped, and chemical changes to these proteins can affect how tightly DNA is packed, influencing gene accessibility and expression. Non-coding RNAs also play a role in regulating the expression of imprinted genes, often acting within specific regions called imprinting control regions (ICRs).
Impact on Health and Development
Genomic imprinting plays a significant role in normal development and growth, particularly influencing embryonic and fetal development. When the imprinting process goes awry, it can lead to specific genetic disorders due to the incorrect expression or silencing of imprinted genes. These disruptions can involve deletions, mutations, or errors in the epigenetic marks themselves.
Two well-known examples of human diseases linked to imprinting defects are Prader-Willi Syndrome and Angelman Syndrome. Both conditions are associated with abnormalities in the same region of chromosome 15 (15q11-13). Prader-Willi Syndrome typically results from the loss of function of paternally expressed genes in this region, leading to characteristics like developmental delay and obesity. Conversely, Angelman Syndrome arises from issues with the maternally expressed gene UBE3A in the same chromosomal area, resulting in severe developmental delays and seizures. Beckwith-Wiedemann Syndrome, characterized by overgrowth and an increased risk of childhood cancers, is linked to abnormal imprinting on chromosome 11, often involving the IGF2 and H19 genes.