UPSC MainsMEDICAL-SCIENCE-PAPER-I202410 Marks
Q19.

Briefly describe the role of Restriction Fragment Length Polymorphism (RFLP) in DNA fingerprinting.

How to Approach

This question requires a focused explanation of RFLP's role in DNA fingerprinting. The answer should begin by defining RFLP and DNA fingerprinting, then detail the process of RFLP – from DNA extraction to visualization of bands. Emphasis should be placed on how variations in restriction enzyme cut sites lead to polymorphic fragments, forming the basis of individual identification. The answer should be concise and technically accurate, suitable for a medical science student.

Model Answer

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Introduction

DNA fingerprinting, also known as DNA profiling, is a laboratory technique used to establish a link between biological material and an individual. It revolutionized forensic science and has applications in paternity testing, disease diagnosis, and species identification. Restriction Fragment Length Polymorphism (RFLP) was one of the earliest and most foundational techniques employed in DNA fingerprinting, predating more modern methods like PCR-based STR analysis. Developed by Alec Jeffreys in 1984, RFLP exploits variations in DNA sequences to create unique genetic profiles.

Understanding RFLP and DNA Fingerprinting

Restriction Fragment Length Polymorphism (RFLP) refers to variations in DNA molecule lengths due to differences in restriction enzyme recognition sites. Restriction enzymes are endonucleases that cut DNA at specific sequences. Polymorphisms, or variations, in these recognition sites lead to different fragment lengths when DNA is digested with the same enzyme in different individuals.

The RFLP Process in DNA Fingerprinting

The process of utilizing RFLP in DNA fingerprinting involves several key steps:

  • DNA Extraction: Genomic DNA is extracted from the sample (blood, saliva, hair follicles, etc.).
  • Restriction Enzyme Digestion: The extracted DNA is then digested with one or more restriction enzymes. The choice of enzyme depends on the level of polymorphism it reveals in the genome.
  • Gel Electrophoresis: The resulting DNA fragments are separated based on size using gel electrophoresis, typically agarose gel electrophoresis. Smaller fragments migrate faster through the gel.
  • Southern Blotting: The separated DNA fragments are transferred from the gel to a membrane (e.g., nitrocellulose or nylon) through a process called Southern blotting. This creates a replica of the DNA fragments on the membrane.
  • Probe Hybridization: A labeled DNA probe, complementary to a specific DNA sequence, is hybridized to the membrane. The probe binds to the DNA fragments containing the target sequence.
  • Detection: The hybridized probe is detected using various methods, such as autoradiography or chemiluminescence. This reveals the location of the DNA fragments containing the target sequence as bands on the membrane.

Interpreting RFLP Patterns

The pattern of bands observed on the membrane represents the individual's DNA fingerprint. Since the length of the fragments depends on the location of restriction sites, variations in these sites between individuals result in different band patterns. These patterns are highly individualistic, allowing for identification. The more restriction enzymes and probes used, the more informative the fingerprint becomes.

Advantages and Limitations of RFLP

RFLP was a groundbreaking technique, but it has limitations:

  • Large DNA Sample Required: RFLP requires a relatively large amount of high-quality DNA, which can be a challenge with degraded or limited samples.
  • Time-Consuming: The entire process, from DNA extraction to detection, is time-consuming, often taking several days to complete.
  • Labor-Intensive: RFLP is a labor-intensive technique requiring skilled personnel.
  • Sensitivity: It has lower sensitivity compared to newer methods like PCR-STR.

Due to these limitations, RFLP has largely been replaced by more efficient and sensitive techniques like Short Tandem Repeat (STR) analysis, which utilizes PCR amplification.

Applications of RFLP

Despite being largely superseded, RFLP still finds applications in specific scenarios:

  • Forensic Science: Historically used in criminal investigations and paternity disputes.
  • Genetic Mapping: Used to map genes and identify genetic markers.
  • Disease Diagnosis: Identifying genetic predispositions to certain diseases.
  • Species Identification: Distinguishing between closely related species.

Conclusion

RFLP played a pivotal role in the development of DNA fingerprinting, providing the initial framework for individual identification based on genetic variations. While largely replaced by more efficient PCR-based methods, understanding the principles of RFLP remains crucial for comprehending the evolution of molecular biology and forensic science. Its legacy continues to influence modern DNA profiling techniques and their applications in diverse fields.

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

Restriction Enzyme
An enzyme that cuts DNA at specific recognition sites, producing DNA fragments of varying lengths. Also known as restriction endonuclease.
Southern Blotting
A technique used to transfer DNA fragments from an agarose gel to a membrane, allowing for subsequent hybridization with a labeled probe.

Key Statistics

Alec Jeffreys estimated the probability of two unrelated individuals having the same DNA fingerprint to be approximately 1 in 7.7 billion in 1985.

Source: Jeffreys, A. J., et al. (1985). "DNA fingerprinting." *Nature*, 316(8208), 76-79.

By the early 1990s, RFLP analysis was being used in over 50 forensic laboratories worldwide.

Source: National Research Council. (1996). *DNA Technology in Forensic Science*. Washington, DC: National Academy Press.

Examples

The Colin Pitchfork Case

In 1986, Colin Pitchfork was the first criminal convicted based on DNA fingerprinting evidence. RFLP analysis linked him to the rape and murder of two young girls in England, demonstrating the power of the technique in forensic investigations.

Frequently Asked Questions

What is the difference between RFLP and STR analysis?

RFLP analyzes variations in the length of DNA fragments created by restriction enzymes, requiring larger DNA samples and being more time-consuming. STR analysis, on the other hand, focuses on variations in the number of short, repetitive DNA sequences (tandem repeats) and utilizes PCR amplification, requiring smaller samples and being faster.

Topics Covered

BiotechnologyGeneticsDNA AnalysisForensic ScienceGenetic Markers