Mutation leading to sickle cell anemia-
**Core Concept**
Sickle cell anemia is a genetic disorder caused by a point mutation in the HBB gene, which encodes the beta-globin subunit of hemoglobin. This mutation leads to the substitution of glutamic acid with valine at position 6 of the beta-globin chain, resulting in the production of abnormal hemoglobin S.
**Why the Correct Answer is Right**
The mutation leads to a change in the conformation of hemoglobin, causing it to polymerize under deoxygenated conditions. This polymerization leads to the formation of sickle-shaped red blood cells, which are rigid and have a shorter lifespan. The sickled red blood cells can get stuck in small blood vessels, leading to tissue ischemia and pain crises. The abnormal hemoglobin S also has a higher affinity for 2,3-bisphosphoglycerate (2,3-BPG), which further exacerbates the polymerization of hemoglobin.
**Why Each Wrong Option is Incorrect**
**Option A:** This option is incorrect because the mutation leading to sickle cell anemia is not a deletion, but rather a point mutation that results in a substitution of glutamic acid with valine.
**Option B:** This option is incorrect because the mutation leading to sickle cell anemia is not a frameshift mutation, but rather a point mutation that results in a substitution of glutamic acid with valine.
**Option C:** This option is incorrect because the mutation leading to sickle cell anemia is not a mutation in the alpha-globin gene, but rather a mutation in the beta-globin gene.
**Clinical Pearl / High-Yield Fact**
Sickle cell anemia is an autosomal recessive disorder, meaning that a person must inherit two copies of the mutated gene (one from each parent) to express the disease. Individuals who inherit one copy of the mutated gene are carriers and may not exhibit symptoms, but can pass the mutation to their offspring.
**Correct Answer:** A. Glutamic acid substitution with valine at position 6 of the beta-globin chain.