125. Which one of the following diseases in caused due to a point mutation in the coding region of
the associated gene?
(a)Hemolyticanemia
(b) Sickle cell anemia
(c) b-thalassemia
(d) a-thalassemia

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Understanding Sickle Cell Anemia: A Point Mutation in the Coding Region

Introduction: Sickle cell anemia is a genetic disorder that affects the red blood cells and is caused by a specific point mutation in the gene that encodes hemoglobin. This disorder is hereditary and results in the production of an abnormal form of hemoglobin called hemoglobin S (HbS), which causes red blood cells to adopt a sickle shape. This article explores how a point mutation in the coding region of the hemoglobin gene leads to the development of sickle cell anemia.

What is Sickle Cell Anemia?

Sickle cell anemia is a type of hemolytic anemia characterized by the presence of sickle-shaped red blood cells. The disease is caused by a single point mutation in the HBB gene, which codes for the beta-globin subunit of hemoglobin. The mutation causes the substitution of glutamic acid with valine at the sixth position of the beta-globin chain. This minor alteration in the protein structure results in the formation of hemoglobin S (HbS), which has reduced solubility, particularly under low oxygen conditions.

The Genetic Basis: Point Mutation in the Coding Region

The genetic mutation that causes sickle cell anemia is a point mutation—a change in a single nucleotide in the DNA sequence of the HBB gene. This gene is located on chromosome 11 and is responsible for producing the beta-globin subunit of hemoglobin. The mutation specifically changes the codon that normally codes for glutamic acid (GAG) to one that codes for valine (GTG).

This point mutation alters the structure of the hemoglobin molecule, making it prone to polymerization when oxygen levels are low. This causes the red blood cells to assume a rigid, sickle shape, which can block blood flow in small vessels, leading to pain, tissue damage, and various complications.

Symptoms and Complications of Sickle Cell Anemia

People with sickle cell anemia can experience a wide range of symptoms, which may vary in severity. Common symptoms include:

• Anemia: The sickle-shaped cells have a shorter lifespan, leading to a constant shortage of red blood cells.

• Painful episodes (Sickle cell crises): These are caused by blockages in small blood vessels, leading to intense pain, especially in the chest, abdomen, and joints.

• Fatigue: Reduced oxygen-carrying capacity of the blood results in fatigue and weakness.

• Organ damage: Recurrent blockages can cause damage to vital organs such as the spleen, liver, and kidneys.

• Increased risk of infections: The spleen, which plays a critical role in fighting infections, may be damaged, increasing susceptibility to infections.

Genetic Inheritance of Sickle Cell Anemia

Sickle cell anemia is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disease. If a person inherits only one mutated gene, they are considered a carrier (heterozygous) and typically do not show symptoms but can pass the mutation on to their children.

The Answer: Sickle Cell Anemia and Point Mutation

The correct answer to the question is sickle cell anemia, which is caused by a point mutation in the coding region of the hemoglobin gene. This single nucleotide change leads to the substitution of glutamic acid with valine in the hemoglobin protein, resulting in the formation of abnormal hemoglobin S.

Conclusion

Sickle cell anemia is a genetic disorder caused by a point mutation in the coding region of the HBB gene, leading to the production of hemoglobin S. This mutation causes red blood cells to adopt a sickle shape, which can obstruct blood flow and lead to a variety of serious health complications. Understanding the genetic basis of sickle cell anemia is crucial for developing treatments and interventions to manage the disease.