Genetics & Inheritance – Topic 2.6 Gene Mutation

These flashcards review definitions, mutation types, molecular consequences, mutagen sources, inheritance patterns, and the molecular basis and physiological effects of sickle-cell anaemia.

What is meant by a gene mutation?

A change in the nucleotide sequence of DNA within a particular gene.

What is meant by a chromosomal aberration?

A mutation that changes the number or structure of whole chromosomes.

What is a point mutation?

A gene mutation involving a change to a single nucleotide pair in DNA.

List the three basic types of DNA sequence change that cause point mutations.

Base-pair substitution, base-pair insertion, and base-pair deletion.

Define a base-pair substitution.

Replacement of one nucleotide and its complementary partner with another pair of nucleotides.

Define a base-pair insertion.

Addition of one nucleotide pair into a DNA sequence.

Define a base-pair deletion.

Removal of one nucleotide pair from a DNA sequence.

What is a missense mutation?

A base substitution that changes a codon so that a different amino acid is inserted into the polypeptide.

How can chemical similarity of amino acids influence the effect of a missense mutation?

If the new amino acid has a similar R group (conservative change), folding and function may be unaffected; if chemically dissimilar (non-conservative), folding and function may be altered, changing phenotype.

What is a nonsense mutation?

A base substitution that converts a sense codon into a premature stop codon, truncating the polypeptide.

Why do nonsense mutations usually produce non-functional proteins?

Translation stops early, yielding a shortened polypeptide that often lacks essential domains for proper folding or activity.

What is a silent mutation and why is it often phenotypically neutral?

A base substitution that changes a codon but not the encoded amino acid due to the degeneracy of the genetic code, leaving the protein unchanged.

Explain a frameshift mutation.

An insertion or deletion not in multiples of three nucleotides that shifts the reading frame, altering every downstream codon.

Why are frameshift mutations typically more severe than single substitutions?

They change many amino acids downstream and may introduce premature stop codons, drastically altering protein structure.

Outline the flow of genetic information affected by mutation (Central Dogma).

DNA mutation → altered mRNA during transcription → altered amino-acid sequence during translation → altered folding → altered protein function → changed phenotype.

Differentiate conservative and non-conservative missense mutations.

Conservative: substituted amino acid has a similar R group, minimal effect; Non-conservative: very different R group, likely alters folding and function.

Give one example of a spontaneous mutation source.

DNA polymerase proofreading error during DNA replication.

What is a mutagen? Give one chemical example.

An agent that increases mutation rate; e.g., ethidium bromide, an intercalating agent.

Name two forms of radiation that can act as physical mutagens.

Ultraviolet (UV) light and X-rays (ionising radiation).

What DNA lesion is commonly produced by UV radiation?

Thymine (pyrimidine) dimers.

Define a germline mutation.

A mutation occurring in gametes or cells that give rise to gametes; it is heritable and present in every cell of the offspring.

Define a somatic mutation.

A mutation occurring in body (somatic) cells; it is not inherited and affects only descendant cells of the mutated cell.

Describe the specific DNA change that causes sickle-cell anaemia.

A single base substitution in the β-globin gene in which T is replaced by A on the template strand.

What codon change occurs in sickle-cell anaemia?

The sixth codon changes from GAA to GUA in the mRNA.

Which amino acid substitution is produced in HbS?

Glutamate (hydrophilic) is replaced by valine (hydrophobic) at position 6 of the β-globin chain.

How does the Glu→Val substitution alter β-globin folding?

Hydrophilic ionic interactions are replaced by hydrophobic interactions, creating a hydrophobic protrusion.

Under what condition do HbS molecules polymerise?

Low partial pressure of oxygen (deoxygenated state).

What is the immediate effect of HbS polymerisation inside red blood cells?

Formation of rigid rod-like fibres that distort the cell into a sickle shape.

Why do sickle-shaped RBCs cause circulatory problems?

They are less elastic, can block narrow capillaries, restrict blood flow and oxygen delivery, leading to tissue damage.

Are individuals with sickle-cell anaemia born with the condition?

Yes, because the causative mutation is inherited in the germline.

Does haemoglobin itself become sickle shaped?

No, the haemoglobin polymerises; the red blood cell becomes sickle shaped.

Which base position in the DNA triplet is often unchanged in a silent mutation and why?

The third (wobble) base, because codon degeneracy often allows different bases at this position to encode the same amino acid.

What happens when a three-nucleotide deletion occurs in a coding region?

One amino acid is removed but the reading frame is preserved; protein may retain partial or full function.

Explain why a frameshift insertion at the start of a gene may generate an immediate nonsense mutation.

The shifted frame can create a premature stop codon shortly after the insertion, terminating translation early.

What type of mutation is created when a mutagenic agent slips between DNA bases, expanding the helix?

Intercalating induction, often causing insertions or deletions leading to frameshifts.

Why is natural selection linked to mutation?

Mutations create new gene variants; beneficial variants may be favoured and spread by natural selection, driving evolution.

Provide one reason nonsense mutations near the gene’s 3′ end may have milder effects than those near the 5′ end.

Truncation closer to the carboxyl terminus removes fewer amino acids, so more of the protein’s functional domains remain intact.

What occurs to sickle-cell red blood cell lifespan and how can this affect the liver?

Lifespan is shortened, increasing RBC turnover; excess breakdown products can overload and damage the liver.