Hemoglobin protein possesses an oxygen-carrying capacity. It occurs in the red blood cells. The functions of hemoglobin include PH maintenance, buffering action, and transportation of carbon dioxide. Hemoglobin is a complex protein. It consists of two main components such as the haem and the globin. Haem transports oxygen. The globin consists of four polypeptide chains. Each polypeptide chain consists of iron-containing haem group. The globin chain protects haem from oxidation. The structure of hemoglobin gets designed in a sophisticated way. Thus, it creates an internal environment of hydrophobicity and protects the iron from oxidation. However, the external structure of hemoglobin helps to get solubilized in water.
Alterations in the structure of hemoglobin lead to abnormalities in hemoglobin structures. These structures possess an affected oxygen-carrying capacity. The term Haemoglobinopathy depicts a condition resulting in disorders related to altered hemoglobin. There are two main categories of Haemoglobinopathies. The first type of hemoglobinopathy arises due to a change in the structure of the hemoglobin chain. The second type of hemoglobinopathy arises due to the synthesis of a faulty globin chain.
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| Image: Genetics of hemoglobinopathies |
What is anemia?
Anemia is a condition leading to a decrease in red blood cells. Thus, the levels of hemoglobin also tend to decrease. Symptoms of anemia include weakness, fatigue, and shortness of breath. Sometimes, the individual may lose consciousness. There are three main types of anemia. Number one type of anemia includes anemia due to blood loss. Second, it occurs due to decreased production of RBCs. The third type of anemia occurs due to an increased breakdown of RBCs. A decreased production of RBCs occurs due to factors such as iron deficiency, vitamin B12 deficiency, and thalassemia. The reason behind the increased breakdown of RBCs is sickling of RBCs due to genetic changes.
The following table shows the types of hemoglobin and the mutations associated with the same.
Types of hemoglobins
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Changes or alterations
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Hemoglobinopathy
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HbS
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A point mutation or an alteration in the beta chain of globin leads to the replacement of glutamic acid to valine amino acid (at the 6th position).
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Sickle cell anemia
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HbC
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A point mutation in the beta-globin genes leads to the replacement of glutamic acid to lysine (at the 6th position).
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Hemolytic anemia,
RBC sickling.
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HbE
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A point mutation in the beta-globin genes leads to the replacement of glutamic acid to lysine (at the 26th position).
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Hemolytic anemia,
RBC sickling.
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Hb Lepore
Hb Anti-Lepore
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Fusion of the delta-beta chains (in Lepore)
Fusion of beta-delta chains (in anti-Lepore)
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Hemoglobin Lepore syndrome
Hemoglobin anti-Lepore syndrome
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Hb constant spring
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Beta-point mutation in the termination codon.
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Hemolytic anemia
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Hb Grady
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Alpha (116-118) duplication mutation.
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Unstable Hemoglobin
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The genetics of Haemoglobinopathies:
Synthesis of hemoglobin takes place either in the mitochondria or cytosol. It occurs through a piece of special genetic machinery. There are two main types of globins such as alpha and beta globins. They get synthesized by alpha and beta globin genes respectively. Specific chromosomes consist of genes responsible for the production of globin chains. Chromosome 16 consists of the genetic code responsible for synthesizing alpha subunit of hemoglobin. Thus it helps in synthesizing alpha chain. Chromosome 11 consists of the genetic code responsible for synthesizing the beta subunit of hemoglobin. Thus, it helps in synthesizing beta chain.
Changes in the globin chain structure affect the formation of hemoglobin. They get associated with diseases such as sickle cell anemia. The changes in the structure of the globin chain occur due to mutations in the globin genes. A mutation either arises spontaneously or gets induced through certain factors. It also occurs due to mutagen exposure. Many types of mutations get observed in globin genes such as point mutations, deletions, insertions or frameshift mutations. Disorders also occur due to alterations in the globin chain synthesis. An example includes thalassemia.
Sickle cell anemia arises due to the changes in the structure of hemoglobin. It leads to hemolytic anemia. Hemolytic anemia is a condition resulting in the elimination of RBC’s from the bloodstream before completing their lifespan. Thus, the survival of RBCs gets reduced. Abnormal hemoglobin leads to sickle-shaped RBC’s with less lifespan. Sickle cell anemia is an example of an autosomal recessive type of inheritance. The RBCs do not look like normal ones. They show crescent-shaped structures. Mutation in the beta polypeptide gene leads to sickle cell anemia. The sickle-shaped cells do not pass through the blood vessels easily. Instead, they get stuck up in the blood vessels. As a result, the oxygen-carrying capacity gets reduced. Sickle cell trait describes the carriers of sickle cell disease. Individuals with the Sickle cell trait show heterozygosity for the mutant gene. The carrier himself will be normal with no symptoms. However, the next generation develops a complete disease.
Thalassaemia also shows the characteristic of hemolytic anemia. In such cases, the globin genes possess normal structures. They synthesize normal globin chains. However, they get produced in fewer amounts.
References:
[1] Hemoglobinopathy-Wikipedia
[2] NCBI
[3] PubMed
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