A 4 year old female child complains of weakness and pain in joints. Her parents are known case of sickle cell trait. Hb electrophoresis reveal HbS pattern. This disease occurs because of which base alteration?
First, I need to recall sickle cell disease's genetic basis. Sickle cell disease is an autosomal recessive disorder caused by a mutation in the beta-globin gene. The specific mutation here is a point mutation where a single nucleotide is changed. The normal beta-globin gene (HBB) has a codon for glutamic acid at position 6, but in sickle cell, it's changed to valine.
Now, glutamic acid is encoded by GAG, and valine by GTG. So the mutation is a substitution of A to T in the second base of the codon. Wait, let me confirm that. The original codon for glutamic acid is GAG. If the sixth amino acid is changed to valine, the codon becomes GUG (if it's a GAG to GTG change). Wait, but GTG codes for valine. So the mutation is a substitution of A to T in the second position of the beta-globin gene's sixth codon. So the base alteration is from A to T, leading to the substitution of glutamic acid to valine.
Looking at the options, the correct answer would be the one stating a single nucleotide substitution in the beta-globin gene, specifically changing the sixth codon from GAG to GTG. Now, the user's options aren't provided, but the correct answer is likely option C or B. However, the user's correct answer is given as [Letter], so I need to structure the explanation accordingly.
The core concept here is the point mutation in the HBB gene leading to sickle cell anemia. The correct answer is the specific base change causing the amino acid substitution. The incorrect options might include other mutations like in alpha-globin, different positions, or other types of mutations like insertions or deletions.
Clinical pearl: Remember that sickle cell is a single nucleotide polymorphism (A to T) in the beta-globin gene. The key is the GAG to GTG change at codon 6.
**Core Concept**
Sickle cell disease results from a **point mutation** in the **beta-globin (HBB) gene** on chromosome 11. This mutation replaces **glutamic acid** with **valine** at the sixth position of the beta-globin chain due to a **single nucleotide substitution** (A→T) in the DNA codon (GAG→GTG).
**Why the Correct Answer is Right**
The mutation occurs at the **sixth codon of the beta-globin gene**, changing **GAG (glutamic acid)** to **GTG (valine)**. This single nucleotide substitution (adenine to thymine) leads to **HbS (sickle hemoglobin)**, which polymerizes under hypoxia, causing erythrocyte sickling. This is a classic example of a **missense mutation** with profound clinical consequences.
**Why Each Wrong Option is Incorrect**
**Option A:** Incorrect if it refers to alpha-glob