In this article we will discuss about the genetics of thalassemia.
There are two main types of thalassemia:
α-thalassemia — resulting from a reduced rate of α-chain;
β-thalassemia — resulting from a defective production of β-chains.
More recently, family studies have revealed a heterogeneity of both α and β- thalassemia which is discussed in the Table 15.1. The β-thalassemias are characterised by persistent δ-chain synthesis beyond the neonatal period, resulting in a variable elevation of foetal hemoglobin.
In some cases β-chain synthesis is totally defective. A similar heterogenity exists in the a-thalassemias.
Since defective a-chain synthesis results in depression of both hemoglobins A and F, and these disorders find expression in both adult and foetal life.
The disease thalassemia is controlled by an allele (C or P thai or a thai) which in homozygous condition produces the severe thalassemia but in heterozygous condition results in a mild form of the disease. The thalassemia allele is widespread mostly in equatorial areas.
The genetics of the α- thalassemias are not yet fully worked out. But it is now quite clear that the clinical results of both types of thalassemia gene (β thal and α thal) i.e. are due to the combined effects of defective globin production and globin-chain imbalance with “inclusion-body” formation (in the absence of sufficient y or β chains, the excess a-chains precipitated forming inclusion body), membrane damage and premature red cell destruction.
Molecular Abnormality:
If is now clear that the thalassemias result from either a partial or total deficit of globin synthesis and this deficit of globin could arise from either a reduced amount of mRNA for a particular chain or from the production of an abnormal mRNA, such that the mechanism of chain assembly i.e. initiation, translation and termination is retarded. Such an abnormality could arise in several ways, h might follow an alteration in a codon such that chain initiation is ineffective.
Alternatively, a t-RNA which is in short supply might be required to insert a given amino acids due to an altered codon anywhere along the m-RNA stand. Finally the chain release mechanism might be abnormal.
Recent studies also indicate that thalassemia is, in fact, a “controller” gene disease, but there are several other theoretical ways in which m-RNA synthesis could be retarded.