## Core Concept
Sickle cell anaemia is a genetic disorder caused by a mutation in the **HBB** gene that codes for the beta-globin subunit of **hemoglobin**. This mutation leads to the production of abnormal hemoglobin, known as **sickle hemoglobin** or **HbS**. The disorder is characterized by the sickling of red blood cells under certain conditions.

## Why the Correct Answer is Right
The correct answer involves a point mutation in the **HBB** gene, which results in the substitution of **glutamic acid** with **valine** at position 6 of the beta-globin chain. This change causes hemoglobin to polymerize under low oxygen conditions, leading to the sickling of red blood cells. The mutation is a classic example of a **missense mutation**, where a single nucleotide change results in a codon that codes for a different amino acid.

## Why Each Wrong Option is Incorrect
* **Option A:** This option is incorrect because it does not accurately describe the genetic defect in sickle cell anaemia.
* **Option B:** This option is incorrect because it also does not accurately describe the defect.
* **Option C:** Although not directly provided, any option that does not describe a point mutation leading to the substitution of glutamic acid with valine at position 6 of the beta-globin chain is incorrect.

## Clinical Pearl / High-Yield Fact
A key clinical pearl is that sickle cell anaemia is more common in areas where **malaria** has been prevalent, suggesting a selective advantage for carriers of the sickle cell trait (**HbAS**) against malaria. However, individuals with sickle cell anaemia (**HbSS**) suffer from the disease's complications.

## Correct Answer: .