Thalassaemia - Genetic errors

Genetic errors that cause Thalassaemia

β-Thalassaemia

Genes for β-globins are located on chromosome 11.
There are over 200 different genetic defects which lead to β-thalassaemia.
Defects are caused mainly by point mutations rather than gene deletions. These result in defects in transcription, RNA splicing and modification, translation via frame shifts and nonsense codons.
The β-globins produced are highly unstable and can’t be used properly.
Either no functional β-globins are produced or they are produced in reduced amounts.

β-thalassaemia major

Both copies of the beta chain gene have mutations, so all haemoglobin are either lacking beta chains or have impaired ones.

β-thalassaemia minor

One copy of the beta chain gene is mutated, one is normal, so therefore enough normal haemoglobin can be produced. People who have this mutation are carriers of it.

α-Thalassaemia

Often caused by gene deletions, although mutations do occur e.g. mutations in stop codons produce α-chains with many more amino acids.
Two copies of the α-chain genes on both chromosomes 16, resulting in total of four genes.
Four-gene deletion, three-gene deletion, two-gene deletion and one-gene deletion can occur.
Either no functional α-chains are produced or they are produced in reduced amounts.

α-thalassaemia major

There is mutation in both copies of the alpha chain gene resulting in either impaired alpha chains being produced or none at all being produced.

α-thalassaemia minor

One copy of the alpha chain gene is mutated, one is normal, so there is enough normal haemoglobin being produced to have little effect on the person. People with this mutation are carriers of it.


Sources

Kumar, P & Clark, M. 2005, Clinical Medicine: A Textbook for Medical Students and Doctors, 6th edn, Saunders, Philadelphia.

http://www.genetics.com.au/factsheet/34.htm 05/04/07