Several mutations influence the synthesis of fetal haemoglobin, HbF, and normal adult haemoglobin, HbA.
• The HbA allele encodes the normal β-globin polypeptide of haemoglobin.
• The HbS allele, which results from a base substitution mutation, encodes an abnormal β-globin polypeptide.
• This base substitution changes the amino acid glutamine, with a polar R group, into valine, with a non-polar R group, in the polypeptide.
The abnormal haemoglobin molecules (HbS) assemble into fibres at low partial pressures of oxygen ($p_{O_2}$).
The fibres make red blood cells sickle shaped and the cells can obstruct blood capillaries.
People whose adult haemoglobin molecules are all abnormal (HbS) have sickle cell anaemia.
This is a painful chronic condition and it can be life-threatening.
(a)[2]
Explain why this mutation leads HbS to form fibres.
(b(i))[2]
Suggest why the British-198 mutation lessens the symptoms of sickle cell anaemia.
(b(ii))[1]
In adults with the British-198 mutation, the gene coding for a fetal haemoglobin polypeptide stays switched on. This is because a protein that regulates gene expression is present.
State the name used for a protein that controls gene expression.
(c(i))[4]
Gel electrophoresis may be used to examine individuals for the different haemoglobin variants: HbA, HbS and HbF.
An alkaline buffer is used so that every haemoglobin molecule becomes negatively charged.
HbS molecules carry one extra positive charge compared with HbA.
Describe and explain how gel electrophoresis is used to diagnose sickle cell anaemia.
(c(ii))[2]
Predict the outcomes for the individuals analysed by drawing bands into lanes 2, 3 and 4 on Fig. 4.1.
Worked solution & mark scheme
This 11-mark question has a full step-by-step worked solution and mark scheme. One marking point: “amino acid changed / non-polar instead of polar” …