Thalassaemia is a genetic disease brought about by the inheritance of faulty genes that code for protein chains making up the haemoglobin protein found in red blood cells. Haemoglobin is made up of four protein chains – two ‘alpha’ (α) globin chains and two ‘beta’ (β) globin chains. Defects in certain genes coding for alpha or beta chains can result in various forms of alpha or beta thalassaemia, depending on which chain is affected. These conditions are classified under the umbrella term haemoglobinopathies. The pattern of inheritance of these genes is autosomal recessive.
Two identical α-globin genes exist on chromosome 16, coding for the alpha chains. Since each person inherits a pair of chromosomes (one from each parent), every person would have four copies of each gene.
Carrier states
- When only one α-globin gene is faulty, the thalassaemia that results does not affect the person, as there are still sufficient mounts of alpha chains are produced by cells. A person with this condition would be known as a silent carrier
- When two faulty α-globin genes are inherited, the carrier may suffer from mild anaemia, but are generally healthy. If the two faulty genes occur on the same chromosome, it is known as alpha zero trait. If they occur at the same loci, it is known as alpha plus trait.
Affected states
- The inheritance of three faulty α-globin genes results in an intermediate form of thalassaemia known as haemoglobin H disease, of HbH. The patient would usually suffer life-long anaemia.
- When all four faulty α-globin genes are inherited, the condition, known as Hb Barts hydrops fetalis, or Alpha thalassaemia major, is fatal to all affected babies, who die soon after birth.
Since there is only one β-globin gene on chromosome 11, every person would inherit two copies of this gene.
- Those with the beta thalassaemia minor condition inherit one faulty β-globin gene, and suffer only from mild anaemia i.e. carrier status
- Beta thalassaemia major suffers have two faulty β-globin genes, and can experience severe anaemia. This condition is also known as Cooley anaemia.
With beta thalassaemia, due to only one gene controlling the production of β-globin chains, inheritance follows an autosomal recessive pattern. For example, a couple who are both carriers of the beta thalassaemia trait will have a 25% chance of having a non-carrier child, 50% chance of having a child who’s a carrier, and a 25% chance of a child with beta thalassaemia major.
The inheritance pattern is slightly more difficult with alpha thalassaemia, due to there being four alpha globin gene copies. However, if one assumes that crossing over doesn’t occur at the α-globin loci, a couple who both posses the alpha zero trait would have a 25% chance of having a child with all four α-globin gene copies, a 50% chance of a child with alpha zero trait, and a 25% of a child with alpha thalassaemia major (Hb Barts hydrops fetalis).
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