Mutations

Types of mutations

1. Substitution

2. Inversion

3. Insertion

4. Deletion

Substitution

Replacement of a nucleotide by another

1 codon is changed

Inversion

Segment of nucleotides separates from allele and rejoins at original position but inverted

Insertion

One or several nucleotides inserted into a sequence, shifts reading frame from point of mutation

Deletion

One of several nucleotides removed from a sequence, shifts reading frame from point of mutation

Frameshift mutation

Insertion or deletion of nucleotides that disrupts the reading frame from point of mutation → produces a non-functional polypeptide

Silent mutation

Mutation that does not change amino acid sequence → no effect on polypeptide structure

Missense mutation

Point mutation where a substitution occurs → leads to a different amino acid being coded for, produces non-functional protein

Nonsense mutation

Point mutation which results in premature stop codon (UAG, UGA, UAA) → polypeptide is truncated

Sickle cell anemia

• Protein affected: beta-globin chain of haemoglobin (HbA to HbS)

• Change:

  • DNA: CTC to CAC

  • mRNA: GAG to GUG

  • Amino acid: glutamate to valine

• Effect of change:

  • Glutamate is negatively charged while valine is hydrophobic

  • Low oxygen, hydrophobic interactions between HbS causes aggregation and forms long rigid fibres

  • Shape of blood cells are distorted and adopt a sickle shape

• Effect of disease:

  • Less flexible and easy breakable cells

  • Poor oxygen transport → anaemia, lack of energy, heart failure

  • RBCs lodge in blood vessels → organ failure

Structural aberrations in chromosomes

1. Deletion

2. Duplication

3. Inversion

4. Translocation

Deletion in chromosomes

• removes chromosomal segment

• EG cri-du-chat syndrome

Duplication in chromosomes

• repetition of a chromosomal segment

• eg charcot-marie-tooth disease

Inversion in chromosomes

• chromosomal segment removed and reinserted in a reversed orientation

• eg haemophilia

Translocation in chromosomes

• movement of a chromosomal segment to another non-homologous chromosome

• eg chronic myelogenous leukaemia

Numerical Aberrations

1. Change in number of chromosomes

   1. Trisomy

   2. Monosomy

2. Result of non-disjunction

   1. Homologous chromosomes don’t move properly to opposite poles in Meiosis I

   2. Sister chromatids fail to separate properly to opposite poles in Meiosis II

Down syndrome (Trisomy 21)

• Result of an extra chromosome 21, hence each body has 47 chromosomes instead of 46

• Most cases result from nondisjunction in Meiosis I

• Characteristic facial features, short stature, heart defects etc