Understanding Sickle Cell Anaemia Genetics

Sickle cell anaemia is a genetic disorder that affects haemoglobin, the protein in red blood cells that carries oxygen. It is inherited in an autosomal recessive pattern. This means that a person must inherit two copies of the mutated gene to have the disease.

The gene involved is for the beta-globin chain of haemoglobin. The normal allele is denoted as $\text{Hb}^\text{A}$, and the allele causing sickle cell haemoglobin is denoted as $\text{Hb}^\text{S}$.

Let's look at the different genotypes and their corresponding phenotypes:

• Genotype $\text{Hb}^\text{A}\text{Hb}^\text{A}$: This is the homozygous dominant genotype. Individuals with this genotype have normal haemoglobin and do not have sickle cell anaemia or the sickle cell trait. Their phenotype is normal.
• Genotype $\text{Hb}^\text{A}\text{Hb}^\text{S}$ (or $\text{Hb}^\text{S}\text{Hb}^\text{A}$): This is the heterozygous genotype. Individuals with this genotype have both normal and sickle haemoglobin. They typically do not have the severe symptoms of sickle cell anaemia but are carriers of the sickle cell trait. They are usually asymptomatic or have mild symptoms under certain conditions. Their phenotype is carrier (sickle cell trait).
• Genotype $\text{Hb}^\text{S}\text{Hb}^\text{S}$: This is the homozygous recessive genotype. Individuals with this genotype have mostly sickle haemoglobin. They develop sickle cell anaemia, which is the diseased phenotype, characterized by sickled red blood cells and various health problems.

Analyzing the Sickle Cell Anaemia Pairs

Now let's evaluate the given pairs based on our understanding of sickle cell anaemia genetics:

• (A) $\text{Hb}^\text{A}\text{Hb}^\text{A}$ : Diseased phenotype

  This statement is incorrect. The $\text{Hb}^\text{A}\text{Hb}^\text{A}$ genotype results in a normal phenotype, not a diseased one.

• (B) $\text{Hb}^\text{A}\text{Hb}^\text{S}$ : Diseased phenotype

  This statement is incorrect. The $\text{Hb}^\text{A}\text{Hb}^\text{S}$ genotype results in the carrier phenotype (sickle cell trait), not the full diseased phenotype of sickle cell anaemia.

• (C) $\text{Hb}^\text{S}\text{Hb}^\text{S}$ : Diseased phenotype

  This statement is correct. The $\text{Hb}^\text{S}\text{Hb}^\text{S}$ genotype is homozygous recessive and causes sickle cell anaemia, which is the diseased phenotype.

• (D) $\text{Hb}^\text{S}\text{Hb}^\text{A}$ : Carrier of disease

  This statement is correct. The $\text{Hb}^\text{S}\text{Hb}^\text{A}$ genotype is the same as $\text{Hb}^\text{A}\text{Hb}^\text{S}$, which represents the heterozygous state. Individuals with this genotype are carriers of the sickle cell trait.

Identifying Correctly Matched Sickle Cell Anaemia Pairs

Based on our analysis, the correctly matched pairs are (C) and (D).

Pair (C) correctly states that the $\text{Hb}^\text{S}\text{Hb}^\text{S}$ genotype corresponds to the diseased phenotype (sickle cell anaemia).

Pair (D) correctly states that the $\text{Hb}^\text{S}\text{Hb}^\text{A}$ (or $\text{Hb}^\text{A}\text{Hb}^\text{S}$) genotype corresponds to the carrier phenotype (sickle cell trait).

Therefore, the option that lists (C) and (D) only as the correctly matched pairs is the correct answer.

Revision Table: Sickle Cell Anaemia Genotype and Phenotype

Additional Information on Sickle Cell Anaemia

Sickle cell anaemia is a classic example of a genetic disorder demonstrating different phenotypes based on zygosity. The $\text{Hb}^\text{S}$ allele arose due to a point mutation in the beta-globin gene, specifically a single nucleotide substitution (A to T) that changes the sixth amino acid from glutamic acid (hydrophilic) to valine (hydrophobic).

Heterozygotes ($\text{Hb}^\text{A}\text{Hb}^\text{S}$), while carriers, have a significant advantage in regions where malaria is prevalent. The sickle trait confers some resistance to malaria, which explains the relatively high frequency of the $\text{Hb}^\text{S}$ allele in these populations despite the severe effects of the homozygous condition ($\text{Hb}^\text{S}\text{Hb}^\text{S}$). This phenomenon is known as heterozygote advantage or balancing selection.

Individuals with sickle cell anaemia ($\text{Hb}^\text{S}\text{Hb}^\text{S}$) can experience various symptoms including chronic pain crises, anaemia, fatigue, increased susceptibility to infections, and organ damage, due to the sickling of red blood cells which obstructs blood flow.