Molecular Characterisation of HBB and associated Polymorphism rs33915217 Involved in Beta Thalassemia

Author Name: *Mowgli Dandamudi, Hemmanur Kavya Chandrika
Author Email: dhmowgli@hotmail.com

Abstract

Mutations in the HBB (Haemoglobin subunit beta) can cause several diseases. β-Thalassemia is one such disease which has no cure. β-Thalassemia can cause abnormal Beta chains in the haemoglobin molecule or in some cases be absent altogether.  Numerous polymorphisms have been identified which can cause β-Thalassemia but one of the more prominent ones is rs33915217. The blood samples form the Diabetic and Healthy individual has been collected and the genomic DNA was extracted. The DNA was further amplified for the SNP region using the specific primers developed using primer3 tool. The amplified products was sequenced and the results are analysed.  Structural analysis of control and test samples have been done and compared to one another. The differences in the structures have been identified and searched for any other occurrences or documentation.

Introduction

Beta-thalassemia (β-thalassemia) is characterized by reduced synthesis of the haemoglobin subunit beta (haemoglobin beta chain) that results in microcytic hypochromic anaemia, an abnormal peripheral blood smear with nucleated red blood cells, and reduced amounts of haemoglobin A (HbA) on haemoglobin analysis. Individuals with thalassemia major have severe anaemia and hepatosplenomegaly; they usually come to medical attention within the first two years of life. Without treatment, affected children have severe failure to thrive and shortened life expectancy. Treatment with a regular transfusion program and chelation therapy, aimed at reducing transfusion iron overload, allows for normal growth and development and may improve the overall prognosis. Individuals with thalassemia intermedia present later and have milder anaemia that only rarely requires transfusion. [1] These individuals are at risk for iron overload secondary to increased intestinal absorption of iron as a result of ineffective erythropoiesis. [2]

Thalassemia occurs when there’s an abnormality or mutation in one of the genes involved in haemoglobin production such as “rs33915217” and many others.

There are three levels of severity in thalassemia that range from mild to severe in their effect on the body.

Thalassemia Minor or Thalassemia Trait: A person with this condition simply carries the genetic trait for thalassemia and will usually experience no health problems other than a possible mild anaemia.

Thalassemia Intermedia: There is a wide range in the clinical severity of this condition, and the borderline between thalassemia intermedia and the most severe form, thalassemia major is confusing. The more dependent the patient is on blood transfusions the more likely he or she is to be classified as thalassemia major.

Thalassemia Major or Cooley’s Anaemia: This is the most severe form of β-Thalassemia in which the complete lack of beta protein in the haemoglobin causes a life-threatening anaemia that requires regular blood transfusions and extensive ongoing medical care. [3]

Signs and symptoms: Iron overload: People with thalassemia can get an overload of iron in their bodies, either from the disease itself or from frequent blood transfusions.

Enlarged spleen: The spleen aids in fighting infection and filters unwanted material, such as old or damaged blood cells. Thalassemia is often accompanied by the destruction of a large number of red blood cells and the task of removing these cells causes the spleen to enlarge. Splenomegaly can make anaemia worse, and it can reduce the life of transfused red blood cells. Severe enlargement of the spleen may necessitate its removal.

Slowed growth rates: Anaemia can cause a child’s growth to slow. Puberty also may be delayed in children with thalassemia.

Heart problems: Diseases, such as congestive heart failure and abnormal heart rhythms, may be associated with severe thalassemia. [3]

Conclusion

The current work focusses on the molecular attributes imparted on the Haemoglobin beta chain of a patient suffering from β-Thalassemia by the Single Nucleotide Polymorphism rs33915217. One type of SNP mutation can cause 2 prominent changes, if not more, as shown in our work. These changes are very directly effective in causing beta thalassemia. One of the changes leads to an extra chain and the other change leads to the absence of a necessary chain. Both of which have been corroborated by other researchers through previous research. Which goes on to show that the same mutation with the same molecular effects has been seen and identified in 3 different parts of the world namely in Iran, America and India. Although no cure exists at the moment for thalassemia, this mutation can be identified before birth of an infant and, should the parents choose, exempt the offspring from a difficult lifestyle.

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