Select the correct match.

Sickle cell anaemia: Autosomal recessive trait, chromosome-11

Phenylketonuria: Autosomal dominant trait

Thalassemia and sickle cell anemia are caused due to a problem in globin molecule synthesis. Select the correct statement.

Thalassemia is due to less synthesis of globin molecules.

Both are due to a qualitative defect in globin chain synthesis.

Both are due to a quantitative defect in globin chain synthesis.

Sickle cell anemia is due to a quantitative problem of globin molecules.

Sickle Cell Anaemia

அரிவாள் செல் இரத்த சோகை

NCERT Class 12 · Principles of Inheritance and Variation · 5 NEET questions

Sickle Cell Anaemia is not just a disease; it is a classic case of point mutation. One single nucleotide substitution changes the entire phenotype. Do not confuse this with chromosomal disorders; this is a gene mutation.

The idea

This is an autosome-linked recessive trait. It occurs due to the substitution of Glutamic acid (GAG) by Valine (GUG) at the sixth position of the beta-globin chain of hemoglobin. This mutation causes the polymerization of hemoglobin under low oxygen tension. Consequently, the RBCs change from biconcave discs to elongated sickle shapes.

Why it matters

It is a qualitative defect in hemoglobin synthesis resulting from a single base substitution (GAG to GUG).

NEET lens

NEET examiners love the GAG to GUG substitution detail. Memorize the exact position: 6th position of the beta-globin chain. Distinguish between the genotype HbA/HbA (normal), HbA/HbS (carrier), and HbS/HbS (diseased). Never mistake this for a sex-linked trait.

Clinical significance

The sickle-shaped RBCs cannot pass through narrow capillaries efficiently, leading to vaso-occlusive crises and severe anaemia. These cells have a significantly reduced lifespan compared to normal RBCs. The body suffers from chronic hypoxia and organ damage due to impaired microcirculation.

Introduction

Sickle cell anaemia is an autosomal recessive hereditary disorder caused by a point mutation (GAG→GTG, glutamate→valine at position 6) in the β-globin gene, producing abnormal hemoglobin S that polymerizes when deoxygenated, distorting RBCs into a sickle shape.

Core concept

Genetics: Autosomal recessive. Mutation: β-globin gene (chromosome 11), codon 6: GAG (Glu) → GTG (Val). HbS (sickle hemoglobin) instead of HbA. Genotypes: HbAHbA: normal. HbAHbS: sickle cell TRAIT (carrier, usually asymptomatic, some sickling under severe hypoxia). HbSHbS: sickle cell ANAEMIA (affected, severely symptomatic). Pathophysiology: Deoxygenated HbS → polymerizes → long fibers → deform RBC → sickle shape → rigid → blood vessel occlusion (vaso-occlusion) → pain crises. Sickled cells: shorter lifespan → haemolytic anaemia. Clinical features: Anaemia (pallor, fatigue). Vaso-occlusive crises: severe pain (bone, chest, abdomen). Stroke. Splenic sequestration. Acute chest syndrome. Increased susceptibility to encapsulated bacteria (especially Pneumococcus) — spleen damaged by repeated sickling. Hydroxyurea treatment: induces HbF (fetal haemoglobin) → reduces sickling.

Go deeper

Sickle cell trait and malaria resistance: HbAS carriers have 10-fold lower mortality from P. falciparum malaria. Mechanism: sickled RBCs in low oxygen of falciparum-infected cells → RBC destruction → parasite killed. This explains why HbS allele has maintained high frequency in malaria-endemic regions (sub-Saharan Africa, India) despite being lethal in homozygous form — heterozygote advantage (balanced polymorphism / overdominance).

From Class 10

Sickle cell anaemia is a genetic blood disorder in which red blood cells are abnormally shaped — like a sickle — causing anaemia and blockages in blood vessels.