What is sickle-cell anaemia? Explain its cause at the molecular level and show how two carrier parents can have an affected child.

1. 1 · Define it. An autosomal recessive Mendelian disorder in which red blood cells become sickle-shaped.
2. 2 · Describe haemoglobin. Four polypeptide chains: two α and two β.
3. 3 · Give the molecular change. Sixth codon of β-globin GAG → GUG; glutamic acid replaced by valine.
4. 4 · Explain the effect. HbS polymerises at low oxygen; red cells change from biconcave discs to sickle shapes.
5. 5 · Work out the cross. [Diagram: HbA HbS × HbA HbS Punnett square; 1 normal : 2 carriers : 1 affected]
6. 6 · Contrast with thalassemia. Thalassemia is a quantitative defect (too little globin); sickle-cell is qualitative (wrong globin).
7. 7 · Link to real life. Carrier screening helps couples know the risk before planning a family.
8. 8 · Close in one line. So a single base change in one gene changes one amino acid and the shape of red blood cells.

Scoring tip: Write GAG → GUG and Glu → Val exactly, and say 'sixth position of the β-chain'. These are the marking points.