UPSC MainsANTHROPOLOGY-PAPER-I202210 Marks150 Words
हिंदी में पढ़ें
Q16.

Genetic imprinting in human diseases.

How to Approach

This question requires a concise explanation of genetic imprinting and its relevance to human diseases. The approach should be to first define genetic imprinting, then explain its mechanism, followed by examples of diseases linked to it. The answer should highlight the atypical inheritance patterns involved and the implications for diagnosis and potential therapies. Structure the response around definition, mechanism, examples, and implications, maintaining brevity within the word limit.

Model Answer

0 min read

Introduction

Genetic imprinting, also known as genomic imprinting, is an epigenetic phenomenon where certain genes are expressed in a parent-of-origin-specific manner. Unlike typical Mendelian inheritance, where both alleles contribute equally, imprinting silences one allele, typically inherited from either the mother or the father. This silencing is achieved through DNA methylation and histone modifications, influencing gene expression without altering the DNA sequence itself. The discovery of imprinting in mice in the 1990s revolutionized our understanding of inheritance and has significant implications for human health, particularly in disease susceptibility.

Understanding Genetic Imprinting

Genetic imprinting is a crucial aspect of human genetics, deviating from standard inheritance patterns. It arises due to epigenetic modifications, primarily DNA methylation and histone modification, which mark specific genomic regions. These marks are established during gametogenesis (egg and sperm formation) and are maintained throughout development. The imprinted status – whether a gene is expressed from the maternal or paternal allele – is "remembered" and passed on to subsequent generations, influencing phenotypic expression.

Mechanism of Imprinting

The process involves two key stages:

  • Establishment: During oogenesis and spermatogenesis, specific DNA sequences are methylated or modified, marking them as imprinted. These marks are then faithfully transmitted to the zygote.
  • Maintenance: These epigenetic marks are maintained through cell divisions, ensuring that the imprinted allele remains silenced.

Imprinted genes often cluster in specific regions of the genome called Imprinting Control Regions (ICRs). These ICRs contain differentially methylated regions (DMRs) that regulate the expression of nearby genes. The DMRs are crucial for establishing and maintaining the imprinted status.

Human Diseases Linked to Genetic Imprinting

Dysregulation of imprinting can lead to various human diseases. Some prominent examples include:

  • Prader-Willi Syndrome (PWS): Caused by a deletion or inactivation of paternal genes on chromosome 15. Affected individuals exhibit hyperphagia (excessive eating), obesity, and developmental delays.
  • Angelman Syndrome (AS): Resulting from a deletion or inactivation of maternal genes on chromosome 15. Symptoms include developmental delay, intellectual disability, seizures, and a characteristic happy demeanor.
  • Beckwith-Wiedemann Syndrome (BWS): A growth disorder often linked to imprinting defects in the 11p15 region. Individuals with BWS experience overgrowth, increased risk of tumors, and other complications.
  • Silver-Russell Syndrome (SRS): Characterized by growth restriction and developmental delay. It's often associated with imprinting abnormalities affecting growth-related genes.

The table below summarizes some key imprinted diseases:

Disease Chromosome Affected Allele Primary Symptoms
Prader-Willi Syndrome 15 Paternal Hyperphagia, Obesity, Developmental Delay
Angelman Syndrome 15 Maternal Developmental Delay, Seizures, Happy Demeanor
Beckwith-Wiedemann Syndrome 11p15 Variable (Imprinting defect) Overgrowth, Tumor Risk

Implications and Future Directions

Understanding genetic imprinting is crucial for accurate diagnosis and genetic counseling. It also provides potential targets for therapeutic intervention. While correcting epigenetic marks is challenging, research into drugs that can modify DNA methylation and histone modifications offers promising avenues for treating imprinting-related disorders. Furthermore, epigenetic inheritance and its role in transgenerational disease transmission are increasingly recognized areas of research.

Conclusion

In conclusion, genetic imprinting represents a fascinating and complex aspect of human inheritance, demonstrating that gene expression isn't solely determined by the DNA sequence itself. Its dysregulation can lead to significant health problems, highlighting the importance of understanding epigenetic mechanisms. Continued research into imprinting promises to improve diagnostic capabilities and potentially develop targeted therapies for related diseases, furthering our understanding of complex genetic phenomena.

Answer Length

This is a comprehensive model answer for learning purposes and may exceed the word limit. In the exam, always adhere to the prescribed word count.

Additional Resources

Key Definitions

Genomic Imprinting
An epigenetic phenomenon where gene expression depends on the parent of origin, leading to different phenotypic outcomes based on whether the gene is inherited from the mother or father.
Imprinting Control Region (ICR)
A genomic region that regulates the expression of nearby imprinted genes. They typically contain differentially methylated regions (DMRs) which are essential for establishing and maintaining imprinting.

Key Statistics

Approximately 100 genes are currently known to be imprinted in mammals, representing about 1% of the mammalian genome.

Source: Knowles, B. B., & Rebmann, T. (2004). Genomic imprinting: mechanisms and implications. <i>Nature Reviews Genetics</i>, <i>5</i>(9), 733-745.

The prevalence of Prader-Willi syndrome is estimated to be 1 in 10,000 to 1 in 20,000 live births.

Source: Prader-Willi Syndrome Association (PWSA) - Knowledge Cutoff

Examples

Prader-Willi Syndrome - A Detailed Example

PWS arises when the paternal copy of a cluster of genes on chromosome 15 is deleted or inactivated. This leads to severe hyperphagia, resulting in morbid obesity if unmanaged. Early management involves strict dietary controls and behavioral interventions.

Frequently Asked Questions

Why is genetic imprinting considered a non-Mendelian inheritance pattern?

Because the phenotypic expression of a gene depends on its parental origin, deviating from the standard Mendelian ratio of 3:1 for dominant and recessive traits.

Topics Covered

GeneticsMedical AnthropologyHealthEpigeneticsImprinting MechanismsDisease DevelopmentInheritance Patterns