• 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?Hb^A

  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,?Hb^S

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.