There are a number of mutations affecting the production of fetal haemoglobin, HbF, and normal adult haemoglobin, HbA. • The HbA allele codes for the normal ẞ-globin polypeptide of haemoglobin. • The HbS allele, caused by a base substitution mutation, codes for an abnormal ẞ-globin polypeptide. • The base substitution results in the amino acid glutamine, which has a polar R group, to be replaced by valine, which has a non-polar R group, in the polypeptide. The abnormal haemoglobin molecules (HbS) form fibres in low partial pressures of oxygen (p02). The fibres cause red blood cells to become sickle shaped and the cells can block blood capillaries. Individuals with adult haemoglobin molecules that are all abnormal (HbS) have sickle cell anaemia.