In sickle cell anaemia-

Options

A. The mutant haemoglobin molecule undergoes polymerisation under low oxygen tension causing the change in the shape of RBC
B. Substitution of Glutamic acid by valine at the sixth position of the `alpha-`chain of haemoglobin
C. The mutant hamoglobin undergoes polymerization under high oxygen tension causing the chage in shape of RBC
D. `alpha-`globin chain is modified

Answer

### Step-by-Step Text Solution:

1. **Understanding Sickle Cell Anemia**: Sickle cell anemia is a genetic disorder caused by a mutation in the hemoglobin gene, specifically affecting the beta-globin chain of hemoglobin.

2. **Identifying the Mutation**: The mutation involves the substitution of the amino acid glutamic acid with valine at the 6th position of the beta-globin chain. This change is a result of a point mutation in the DNA sequence.

3. **Effects of Low Oxygen Tension**: Under low oxygen conditions, the mutant hemoglobin (HbS) tends to polymerize, leading to the distortion of red blood cells (RBCs) into a sickle shape. This sickling of cells can cause blockages in blood vessels and lead to various complications.

4. **Analyzing the Options**:
- **Option 1**: Correctly states that the mutant hemoglobin undergoes polymerization under low oxygen tension.
- **Option 2**: Incorrectly states that glutamic acid is replaced by valine at the 6th position of the alpha chain; it actually occurs in the beta chain.
- **Option 3**: Incorrectly states that polymerization occurs under high oxygen tension; it occurs under low oxygen tension.
- **Option 4**: Incorrectly states that the alpha globin chain is modified; the defect lies in the beta globin chain.

5. **Conclusion**: The correct answer is that the mutant hemoglobin undergoes polymerization under low oxygen tension, which leads to the sickling of RBCs.