Epigenetics Research: Open Access
Open Access

Understanding Genomic Imprinting and its Impact on Disease and Health

Fuying Yu^{* *}Correspondence: Fuying Yu, Department of Biological Sciences, Nanyang Technological University, Queenstown, Singapore, Email:

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Description

Genomic imprinting is an interesting genetic phenomenon where the expression of certain genes depends on whether they are inherited from the mother or the father. Unlike typical inheritance, where both copies of a gene from each parent are expressed equally, imprinted genes are subject to parent-of-origin specific expression. This means that one allele, either the maternal or paternal, is silenced through epigenetic mechanisms, such as DNA methylation or histone modifications. Disruptions in this delicate process can lead to a variety of diseases, some of which are severe and life altering.

Mechanism of genomic imprinting

At the molecular level, genomic imprinting occurs due to epigenetic modifications that alter the expression of genes without changing the DNA sequence itself. These modifications affect the chromatin structure and can silence one allele while allowing the other to remain active. Imprinting is typically reset during gamete formation, ensuring that the proper imprinting marks are passed on from parents to offspring. While most genes are expressed from both alleles, imprinting affects only a small subset of genes, typically involved in growth, development, and metabolism. Imprinted genes are found in regions of the genome where their parent-specific expression plays a critical role in regulating the growth and function of tissues during fetal development.

Imprinting disorders and their impact

Disruptions in genomic imprinting can lead to a variety of disorders, often involving complex interactions between genetics and environmental factors. Two of the most well-known imprinting disorders are Prader-Willi Syndrome (PWS) and Angelman Syndrome (AS), both of which arise from deletions or mutations in the same chromosomal region but manifest differently due to the parent-of-origin effect.

PWS: This disorder occurs when the paternal copy of the chromosome 15 is deleted or mutated, leading to developmental delay, intellectual disability, obesity and hormonal imbalances. In PWS, the absence of the normally active paternal genes causes the symptoms associated with the disorder.

AS: In contrast, Angelman syndrome arises from a similar chromosomal region on chromosome 15 but involves a mutation or deletion of the maternal copy. Severe developmental delays, speech impairments, seizures and a happy, excitable demeanor characterize this syndrome. In AS, the loss of the maternal allele's expression leads to the clinical features observed.

These two disorders illustrate how the same genetic region can lead to different diseases depending on whether the mutation or deletion is inherited from the mother or the father. This phenomenon highlights the critical role that genomic imprinting plays in human development.

Other imprinting-related diseases

While PWS and AS are the most studied, several other diseases have been linked to genomic imprinting. For instance, Beckwith- Wiedemann Syndrome (BWS), which involves overgrowth and an increased risk of cancer, results from abnormal imprinting on genes related to cell growth. BWS is typically caused by the overexpression of the paternal allele or loss of maternal imprinting of certain growth-regulating genes. Additionally, Silver-Russell Syndrome (SRS), a disorder characterized by growth restriction, is caused by defects in imprinting control regions. SRS patients often exhibit asymmetry of the body, feeding difficulties and delayed development.

Conclusion

Genomic imprinting is an important aspect of our genetic makeup that controls the expression of specific genes based on their parental origin. When this process goes awry, it can lead to a variety of imprinting disorders, each with unique symptoms and clinical features. Understanding the mechanisms behind genomic imprinting is vital not only for diagnosing these conditions but also for developing potential therapies and interventions. As research in this area continues to evolve, it holds the potential of improving our understanding of these complex diseases and preparing for targeted treatments that address the root causes of imprinting-related disorders.