Question

Write the types and locations of the genes causing thalassemia in humans. State the cause and symptoms of the disease. How is sickle-cell anemia different from this disease ?

Hint:

Name the alpha (chromosome 16) and beta (chromosome 11) types, then say thalassemia is low globin synthesis while sickle-cell is a structural Glu to Val change.

Answer 1

Step 1: Name the two types and the gene locations:
Thalassemia is an autosomal recessive blood disorder. It is a Mendelian disease, so it passes from parents to children through autosomes.
There are two types, named after the globin chain that is made in lower amounts: \(\alpha\)-thalassemia and \(\beta\)-thalassemia.
\(\alpha\)-thalassemia is controlled by two closely linked genes, HBA1 and HBA2, on chromosome 16. Each parent gives one copy of this gene pair.
\(\beta\)-thalassemia is controlled by a single gene, HBB, on chromosome 11 of each parent.

Step 2: State the cause:
The cause is a mutation or deletion in the globin gene. The mutation lowers the rate of synthesis of either the \(\alpha\) chain or the \(\beta\) chain of haemoglobin.
Adult haemoglobin needs two \(\alpha\) and two \(\beta\) chains in equal numbers. When one chain is made less, the balance is lost.
The extra, unpaired chains are unstable and damage the red blood cells. Fewer normal haemoglobin molecules are formed.

Step 3: State the symptoms:
The red cells are small and break early, so the person becomes anaemic.
Common signs are pale skin, tiredness, weakness, shortness of breath and slow growth in children.
In severe cases there is jaundice and an enlarged spleen. The patient may need repeated blood transfusion.

Step 4: Compare with sickle-cell anemia:
Thalassemia is a quantitative defect. The globin chain has a normal structure, but too little of it is made, so the amount of haemoglobin falls.
Sickle-cell anemia is a qualitative defect. A single base change (GAG to GTG) in the \(\beta\)-globin gene replaces glutamic acid by valine at the sixth position of the \(\beta\) chain.
This structural change gives an abnormal haemoglobin, HbS. In low oxygen, HbS polymerises and bends the red cell into a sickle shape.
Sickle-cell anemia is also an autosomal recessive disease and its gene is also on chromosome 11, but it is a point mutation and not a fall in chain synthesis.

Final Answer:
Thalassemia is a reduced-synthesis (quantitative) defect of globin chains, while sickle-cell anemia is a structural (qualitative) defect of the \(\beta\) chain.