Genetics of Thallasemia

Thalassemia is a type of inherited blood disorder that causes a reduction in the production of an oxygen carrying protein in blood cells called hemoglobin (Hb).

The structure of hemoglobin is subdivided into 4 parts which include 2 α chains (HbA) and 2 β chains (HbB) both genes are located on chromosome 16 and chromosome 11 respectively.

Globally, about 56000 of 332000 births affected with hemoglobin disorders will have one form of thalassemia. It is the most common inherited single-gene disorder in the world with especially high prevalence in countries where malaria is endemic.

Mode of Genetic Inheritance of Thalassemia

Thalassemia is inherited in an autosomal recessive pattern which means the mutated genes that will cause this blood disorder is located on the autosomal chromosomes (11 and 16).

two copies of the same mutated gene has to be present for the disease to develop. It is also a single gene disorder where the mutation will only affect the expression of one specific gene as compared to a complex cluster of genes.

There are two main categories of thalassemia; β – thalassemia and α – thalassemia.

β – thalassemia is caused by point mutations (insertion, deletion or change in a single nucleotide base) that results in defective production of β – globin chains.

Whereas, α – thalassemia occurs when there are gene deletions in the α – globin gene. The mutations in both types of thalassemia will cause reduced production of its respective globin protein and a relative excess of the other protein.

Without proper functioning globin proteins, there will be more abnormal precursor cells in the bone marrow and will reduce normal red blood cell production. The low production of red blood cells will result in various signs and symptoms of anemia which include dizziness, paleness, dark urine, and jaundice.

Types of Thalassemia

β – thalassemia

β – thalassemia is caused by the deficiency or absence of β – globin, resulting in relative excess of α – globin. Mutations of the β – globin gene are divided into two groups;

β0 mutations where β-globin synthesis is absent, and β+ mutations where β-globin synthesis is delectably lower.

Below is the table illustrating the different mutations on β – globin gene that cause the various sub types of β – thalassemia.

β – thalassemia

Mutation on chromosome 11 Clinical attributes


Only one type of β – globin gene mutation (heterozygous carriers) (β0/β), (β+/β) No symptoms; some cases can show mild forms of anaemia and some abnormal red blood cells


Variable of two β – globin gene mutations Mild to severe; regular blood transfusion not required


Two β – globin gene mutations (Homozygous)

0/ β0), (β+/ β+), (β+/ β0)

Severe; Blood transfusion required

Legend: β (normal gene), β0, β+ (mutated gene)

α – thalassemia

α – thalassemia results from the reduction or absence of α – globin and causes the relative excess of β – globin. There are 4 α – globin genes two on each chromosome 16 and the deletion mutation in one of more of the genes can develop one form of α – thalassemia.

In the table below are the different clinical attributes of the different types of mutations in α – globin genes.

α – thalassemia

Mutation on chromosome 16 Clinical attributes

Silent carrier

Single α – globin gene deletion No symptoms; normal red blood cells

α – thalassemia trait

Deletion of two α – globin genes No symptoms; will have mild anaemia

HbH disease

Deletion of three α – globin genes Severe; regular blood transfusion not required

Hydrops fetalis

Deletion of all four α – globin genes Fatal to the foetus if no blood transfusion is given

HbH – Haemoglobin H disease which is most common in Asian populations. It usually causes microcytic anemia, jaundice, and splenomegaly.

Hydrops fetalis : A fatal condition for a fetus characterized by pallor, generalized edema, and massive hepatosplenomegaly. If intrauterine blood transfusion is not administered it can cause sever tissue anoxia leading to stillbirth.

With the inheritance pattern of thalassemia genetic tests are available during pregnancy to determine whether your baby has thalassemia and its severity. A sample is taken either by chronic villus sampling from the placenta at the 10th to 12th week of pregnancy or by fetal blood sampling from the umbilical cord around 18 to 10 weeks of pregnancy.

Genetic counseling is also available for anyone planning to have a baby and have family history of thalassemia or suspect that either parent may be carriers.