Sickle cell anemia is the clinical manifestation of homozygous genes for an abnormal haemoglobin molecule. The event responsible for the mutation in the b chain is:
**Core Concept**
Sickle cell anemia is a genetic disorder caused by a mutation in the HBB gene, which codes for the beta-globin subunit of hemoglobin. This mutation leads to the production of abnormal hemoglobin S (HbS), characterized by a substitution of glutamic acid with valine at the sixth position of the beta-globin chain. This substitution causes hemoglobin S to polymerize under low oxygen conditions, resulting in sickling of red blood cells.
**Why the Correct Answer is Right**
The mutation responsible for sickle cell anemia is a point mutation, specifically a nucleotide substitution, in which adenine (A) is replaced by thymine (T) at the 5th codon of the HBB gene. This substitution leads to the substitution of glutamic acid with valine at the sixth position of the beta-globin chain, resulting in the production of abnormal hemoglobin S (HbS).
*Option A:* This option is not directly related to the mutation responsible for sickle cell anemia. While it is true that sickle cell anemia is caused by a mutation in the HBB gene, option A does not specify the type of mutation or the location of the mutation.
**Why Each Wrong Option is Incorrect**
*Option B:* This option is incorrect because it does not specify the type of mutation or the location of the mutation responsible for sickle cell anemia. While it is true that sickle cell anemia is a genetic disorder, option B is too vague and does not provide any specific information about the mutation.
*Option C:* This option is incorrect because it is not a specific type of mutation. While point mutations can cause a variety of genetic disorders, option C is too general and does not provide any specific information about the mutation responsible for sickle cell anemia.
*Option D:* This option is incorrect because it is not a specific location of the mutation. While the HBB gene is involved in sickle cell anemia, option D does not specify the location of the mutation within the gene.
**Clinical Pearl / High-Yield Fact**
The sickle cell mutation is a classic example of a "missense" mutation, where a point mutation in the DNA sequence leads to a substitution of one amino acid for another in the protein sequence. This type of mutation can have significant consequences for the function of the protein and can lead to a variety of genetic disorders.
**Correct Answer:** C. A nucleotide substitution in the HBB gene.