• A?gene mutation?is a change in the sequence of base pairs in a DNA molecule; this may result in a new allele
  • Mutations occur?all the time?and?at random
  • There are certain points in the cell cycle when mutations are more likely to occur, for example,?copying errors?when DNA is being replicated (S phase of interphase)
• As the DNA base sequence determines the sequence of amino acids that make up a polypeptide,?mutations in a gene?can sometimes lead to a?change in the polypeptide?that the gene codes for
• Most mutations are?harmful?or?neutral?(have no effect) but some can be?beneficial
• Inheritance?of mutations:
  • Mutations present in normal body cells are?not inherited, they are eliminated from the population once those cells die
  • Mutations within?gametes?are inherited by offspring, possibly causing genetic disease

Substitution mutations

• A mutation that occurs when a base in the DNA sequence?is randomly swapped?for a different base is known as a?substitution mutation
• A substitution mutation will only change the amino acid for the triplet (group of three consecutive bases) where the mutation occurs; it will?not have a knock-on effect?further along the gene/polypeptide

An example of a substitution mutation altering the sequence of amino acids in the polypeptide

• A small change to a gene can have?serious consequences?for an organism
• Sickle cell anaemia is a genetic disease caused by?a single base substitution mutation?within the gene (Hb) that codes for the alpha-globin polypeptide in haemoglobin
  • Most humans have the normal allele?HbA

The mutation that occurs

• Within the haemoglobin gene, the base thymine (T) is?replaced by the base adenine?(A). This causes the DNA triplet GAG to mutate to GTG
• The mutated DNA codon GTG is transcribed into the?mRNA codon GUG, instead of GAG
• During translation the amino acid?valine?(VAL) replaces the original amino acid?glutamic acid?(GLU); this occurs on the?sixth position?of the polypeptide
• The slightly different polypeptide results in a new allele,?HbS

A base substitution on the DNA molecule results in a change in the amino acid at position 6 of the haemoglobin polypeptide, altering the overall structure and function of the protein

The effects

• The protein haemoglobin?S?is produced instead of haemoglobin A; this causes a?distortion in the shape of the red blood cells?into?sickle shapes
• Sickle-shaped red blood cells:
  • Have a?limited oxygen-carrying capacity
  • Block the capillaries?limiting the flow of normal red blood cells
• People with sickle cell anaemia suffer from?acute pain,?fatigue?and?anaemia
• There is a?correlation?between?sickle cell anaemia?and?malaria
  • In areas with increased malaria cases, there is an increased frequency of sickle cell alleles

Normal red blood cells and sickle cell blood cells. The sickle cells cause a blockage in the capillary, restricting blood flow.