6.1.2 - Point and Chromosomal Mutations

Question 1

Point mutation

Answer 1

• A variation in a single nucleotide that occurs due to base substitution or the insertion or deletion of a nucleotide
• E.g. sickle cell gene point mutation: CTC is changed to CAC. This changes the amino acid glutamate into valine, altering the shape of the haemoglobin molecule and resulting in blood cells having a sickle shape

Question 2

Frameshift mutation

Answer 2

• The insertion or deletion of a nucleotide (not in multiples of 3) shifts the entire “reading frame” of RNA codons. This causes run-on alteration of a whole nucleotide sequence, resulting in incorrect amino acids being assembled into the polypeptide chain. The end result is the production of a non-functional protein

Question 3

Types of point mutations

Answer 3

Nonsense:

• An amino acid is changed into a stop codon, resulting in the premature conclusion of polypeptide synthesis. This causes the protein to be shorter than it should be, and non-functional. Has a major phenotypic effect

Missense:

• An amino acid is changed into another acid, for example in epidermolysis bullosa, G is substituted for T at nucleotide 6724 in exon 85, causing tryptophan to replace glycine at that codon in the collagen protein produced.
• The resultant protein could still be functional, depending on whether the replacement amino acid is the same type as the original

Silent:

• Changes in the DNA sequence that have no effect on the amino acids assembled. This is because the particular amino acid may be associated with multiple different codons, so the altered codon is still able to code for the same amino acid
• Due to this, silent mutations have no noticeable effect on the phenotype

Note: these mutation can also be caused by insertion or deletion, but are typically caused by base substitutions.

Question 4

Neutral mutation

Answer 4

• A broad term for mutations that do not affect protein function
• Can occur in any part of the genome, including both introns and extrons
• Can change an amino acid in a way that doesn’t change protein function
• Silent mutation is an example of a neutral mutation, as the mutation has no impact on the organism’s phenotype

Question 5

Chromosomal mutations

Answer 5

• Mutations where genes are moved to other parts of a chromosome
• Usually occurs during cell replication in meiosis or mitosis
• Can be structural (deletion, duplication, inversion, or translocation), or numerical (aneuploidy or polyploidy)

Question 6

Types of structural chromosomal abnormalities

Answer 6

Deletion:

• Part of a chromosome breaks off and is lost (does not attach elsewhere)
• This can occur during recombination if the homologous chromosomes are misaligned, as there will be an unequal exchange of genetic material between the paternal and maternal chromosomes

Duplication:

• Two copies of the same section are present on a chromosome
• Can occur during recombination due to misalignment of homologous chromosomes, which leads to an unequal exchange of genetic material
• Can also occur due to replication slippage: DNA polymerase duplicates a segment of the chromosome

Inversion:

• Part of a chromosome breaks off and reattaches in the opposite direction, reversing the order of genes
• If “balanced”: no deterious effect
• If one or both breaks in the DNA fall within the reading frame of a gene, it can no longer be read, potentially causing a loss of function.

Translocation:

• Occurs when a segment of chromosome is moved to another, non-homologous chromosome

Question 7

Numerical chromosomal abnormalities

Answer 7

• The number of chromosomes in a cell is abnormal, i.e. there are less or more chromosomes than the normal karyotype
• Comprises aneuploidy and polyploidy

Question 8

Aneuploidy

Answer 8

• An abnormal number of chromosomes in cells
• E.g. trisomy, when an extra copy of only one chromosome is made. For example, the presence of an extra chromosome 21 in autosomes results in trisomy 21, the cause of Down’s syndrome
• E.g. monosomy, when a copy of one chromosome is missing
• Commonly caused by nondisjunction during meiosis or mitosis, though this is not the only cause

Question 9

Polyploidy

Answer 9

• An extra copy of every chromosome in the karyotype is present
• Common in plants, and some polyploid plants are larger, stronger, and more disease-resistant than others while still being able to reproduce normally
• Rare in animals as they usually fail to develop

In humans, this can lead to cells being 3n, 4n, etc.