Lesson 3 of 9 / Mutation, cell division and cancer
From one substitution to sickling
How can one changed amino acid affect a whole cell?
I can explain how a gene mutation can cause disease using sickle cell anaemia.
I can explain mutation-caused disease, including sickle cell anaemia.Syllabus
Syllabus 8876, Core 2(e). Explain mutation-caused disease, including sickle cell anaemia.
About 5 min
Make a guess. You are not marked.
Sickle-cell disease comes from one base substitution. Does it shift every later codon?
Show the answer
One codon and one amino acid change.
A substitution keeps the reading frame. The single changed amino acid alters how haemoglobin molecules interact.
The key idea
A substitution in the beta-globin gene changes an amino acid, altering haemoglobin interactions and potentially red-cell shape and survival.
Explore the idea
Keep the sequence; change oxygen conditions
The genotype is not changing with oxygen. Oxygen conditions affect the behaviour of the altered haemoglobin; this is an illustrative cell, not a clinical prediction.
Explanation
The sickle-cell allele changes the beta-globin sequence so that valine replaces glutamic acid at a particular position. In a coding-strand example, GAG becomes GTG; the corresponding mRNA codon changes from GAG to GUG. This is a base substitution, not a frameshift.
Valine is hydrophobic whereas glutamic acid is charged under normal cellular conditions. This changes the surface properties of the haemoglobin subunit. Under low-oxygen conditions, haemoglobin S molecules can associate into fibres, making affected red cells less flexible and sickle-shaped.
Less flexible cells can obstruct small vessels, reducing blood delivery. Affected red cells are also broken down more rapidly, contributing to anaemia. The disease therefore reflects a chain of effects from DNA through protein interaction to cell behaviour and tissue function.
An allele's effect depends on genotype and conditions. The homozygous sickle-cell genotype has different consequences from the usual heterozygous trait. Do not infer that one changed base always causes the same disease or that every mutation has a major effect.
Step by step
- 1
DNA to amino acid
A codon change replaces glutamic acid with valine in beta-globin.
- 2
Amino acid to interaction
Altered surface properties promote haemoglobin aggregation under suitable conditions.
- 3
Cell to organism
Reduced flexibility, blockage and shortened cell survival affect blood function.
Worked example
Improve an incomplete answer
A student writes, "The mutation changes red-cell shape." Add the missing molecular steps.
One way to explain it
The substitution changes the beta-globin amino-acid sequence, replacing glutamic acid with valine. Altered surface properties allow haemoglobin S to form fibres under low oxygen, which distort the red cell and reduce flexibility.
Why this answer works
- Name the protein intermediate.
- Explain how a chemical change affects molecular association.
- Then connect the association to the cell.
Watch out for this
A student says: "The sickle-cell substitution shifts every later codon." What is wrong with this?
Show the answer
A substitution changes a base without adding or removing one, so the reading frame remains. The important effect is the changed amino acid and protein interaction.
Check your understanding
Which causal order is appropriate?
Show the answer
DNA substitution, changed beta-globin, altered aggregation, less flexible cells.
This connects molecular information to the cellular effect.
Quick recall
How can one changed amino acid affect a whole cell?