top of page
Search

MRCP Genetics: Molecular Techniques (PCR, FISH)

TL;DR

MRCP Part 1 genetics commonly tests molecular techniques such as PCR and FISH at a clinical-application level. You are expected to know what each test detects, when to use it, and its limitations, rather than laboratory protocols. This article covers the exact scope, high-yield facts, classic traps, and exam-style examples you need to score safely in molecular genetics.


Why this matters in MRCP Part 1

Molecular genetics questions in MRCP Part 1 are usually short, deceptively simple, and highly discriminating. They often appear as one- or two-line clinical vignettes asking for the most appropriate investigation, rather than diagnosis. Candidates who revise genetics superficially tend to default to “PCR” for everything—an error the exam exploits repeatedly.

The exam blueprint published by MRCP(UK) confirms that candidates are expected to understand basic molecular techniques and their clinical relevance, not bench-side detail. If you are revising genetics as part of your wider MRCP Part 1 overview, mastering these techniques can convert an otherwise weak area into easy marks.


Scope of molecular genetics tested

MRCP Part 1 focuses on:

  • DNA-based diagnostic techniques

  • Detection of mutations, deletions, duplications, and translocations

  • Choosing the right test when karyotype is normal

  • Understanding why a test may fail in a given condition

It does not test primer design, buffer solutions, or laboratory workflow.


High-yield molecular techniques (numbered list)

  1. PCR (Polymerase Chain Reaction) amplifies a known DNA sequence exponentially.

  2. PCR requires prior knowledge of the target sequence.

  3. RT-PCR involves reverse transcription of RNA to DNA.

  4. Quantitative PCR (qPCR) measures DNA/RNA quantity in real time.

  5. FISH (Fluorescence In Situ Hybridisation) detects specific chromosomal regions using fluorescent probes.

  6. FISH works on interphase nuclei and does not require dividing cells.

  7. Southern blotting detects large DNA fragments and repeat expansions.

  8. PCR is unreliable for large trinucleotide repeat expansions.

  9. MLPA identifies copy-number changes (small deletions/duplications).

  10. Comparative genomic hybridisation (CGH) analyses genome-wide copy number.

Memorising this list alone answers a significant proportion of MRCP Part 1 genetics questions.


The five most tested subtopics

1. PCR – core principles

PCR amplifies DNA using repeated cycles of denaturation, annealing, and extension. In MRCP Part 1, it is commonly tested in the context of single-gene disorders and infectious diseases.

Exam pearl: PCR is extremely sensitive but prone to contamination.

2. Quantitative PCR (qPCR)

qPCR allows quantification of nucleic acid. Clinically, it is used to monitor viral load (e.g. HIV, hepatitis B/C) and oncogene amplification.

Exam pearl: qPCR provides quantity, not just presence.

3. FISH

FISH uses fluorescent probes that bind to specific chromosomal loci. It is ideal for detecting microdeletions and translocations invisible on standard karyotyping.

Exam pearl: Best test when phenotype suggests a deletion but karyotype is normal.

4. Southern blotting

Although largely replaced clinically, Southern blotting remains examinable because it explains why PCR fails in trinucleotide repeat disorders such as Huntington disease.

Exam pearl: Think Southern blot when repeats are very large.

5. Copy-number techniques (MLPA / CGH)

These methods detect submicroscopic deletions and duplications across the genome.

Exam pearl: Use when suspicion remains despite normal karyotype.


Comparison of PCR and FISH techniques for genetic diagnosis in MRCP Part 1.

One-look comparison table

Technique

Detects

Typical MRCP use

PCR

Specific DNA sequence

Single-gene disorders

qPCR

DNA/RNA quantity

Viral load monitoring

FISH

Chromosomal location

Microdeletions

Southern blot

Large DNA fragments

Repeat expansion disorders

MLPA

Copy-number change

Submicroscopic deletions


Practical mini-case (exam style)

Question: A child has learning disability, congenital heart disease, and hypocalcaemia. Routine karyotype is normal. Which test confirms the diagnosis?

Best answer: FISH

Explanation: This presentation suggests 22q11 deletion syndrome. The deletion is too small for karyotyping. FISH is specifically designed to detect such microdeletions. PCR would only help if the exact gene mutation were already known.

You can practise similar genetics questions using timed blocks in a high-quality MRCP question bank.


Common pitfalls (5 classic traps)

  • Choosing PCR when the mutation is unknown.

  • Forgetting that FISH works on non-dividing cells.

  • Using karyotype for suspected microdeletion syndromes.

  • Confusing PCR with qPCR.

  • Ignoring why PCR fails in repeat-expansion disorders.

Practical study-tip checklist

  • Link one condition to one test while revising.

  • Study molecular genetics alongside chromosomal disorders.

  • Use mixed-topic question blocks, not isolated reading.

  • Review every genetics error in detail—patterns repeat.

  • Re-test using full-length mock exams before the real paper.


FAQs (People Also Ask)

Is PCR enough for most MRCP Part 1 genetics questions?

No. Many questions are designed so PCR is not the correct answer, especially in microdeletion syndromes.

When should I choose FISH over karyotyping?

When the clinical phenotype is strong but the karyotype is normal.

Do I need to know PCR cycles in detail?

No. Understanding the principle and clinical application is sufficient.

Are next-generation sequencing techniques tested?

Only at a very superficial level; detailed interpretation is uncommon in MRCP Part 1.


Ready to start?

Molecular genetics becomes straightforward once you focus on test selection rather than theory. Consolidate this topic within the official MRCP Part 1 syllabus, practise regularly with high-quality MCQs, and stress-test your understanding using realistic mock exams before exam day.


Sources

 
 
 

Comments

bottom of page