Hemoglobin Variants are different types of hemoglobin that occur due to mutation of hemoglobin. Hemoglobin is found in the blood and tissues of both human and animals. Because of the genetic differences between different species, species have their own Hemoglobin Variants.
While mutation of Hemoglobin may sound as an abnormal condition, mutation of Hemoglobin occurs normally during the different stages of human body development. The normal Hemoglobin Variants of each stage are beneficial for the physiological function of human blood at that stage. On the other hand, due to genetic disorders, abnormal mutation of human hemoglobin may occur leading to abnormal Hemoglobin Variants to be found in human blood. While some of those abnormal Hemoglobin Variants may not have a noticeable effect on human health, other abnormal Hemoglobin Variants may cause diseases.
Hemoglobin Levels Normal Hemoglobin Levels Normal Alternations to Hemoglobin Levels Causes of Low Hemoglobin Levels Causes of High Hemoglobin Levels Hemoglobin Variants Benefits of having different Hemoglobin Variants Genetics and structure of Hemoglobin Variants Normal Hemoglobin Variants Embryonic Hemoglobin Hemoglobin Gower 1 Hemoglobin Gower 2 Hemoglobin Portland 1 Hemoglobin Portland 2 Fetal Hemoglobin (Hemoglobin F) Hemoglobin F Normal Levels Function of Hemoglobin F Adult Hemoglobin (Hemoglobin A) Hemoglobin A1 Hemoglobin A2
There is a good reason for Hemoglobin to be mutatable and for human beings to have different Hemoglobin Variants. Hemoglobin variants have different biochemical characteristics the enable each hemoglobin variant to function differently when it comes to binding with Oxygen, Carbon Dioxide, and other ligands .
Mammals and most species, including humans, inherit genetic characteristics from their parents. That means the cells of a human fetus are expected to have a genetic code different from the genetic code of the mother’s cells. On the other hand, White Blood Cells that circulate within the mother’s blood are there to attack foreign bodies that don’t have the same genetic code the mother’s cells have. For this reason, human fetuses have their own blood which circulates all over their body to provide the necessary Oxygen and nutrition to their growing cells and tissues. If the mother’s blood mixes with the fetus blood or circulates inside the fetus body, the mother’s immune system will fight against the fetus as if it is a foreign invading body and the mother’s White Blood Cells will attack the blood cells of the fetus and any of the fetus’ cells and tissues they have access to.
Human fetuses don’t use their respiratory system while inside the mother’s uterus. The first time the respiratory system is used when a new born starts crying immediately after birth.
Before birth, nutrition and Oxygen are transferred from the mother’s blood to the fetus blood via the umbilical vein. The Chorion stands as a barrier between the mother’s blood and the fetus’ blood preventing the blood cells and plasma from passing and allowing only the smaller molecules of Oxygen and other ligands to pass.
For gases, and fluids as well, to move from point A to point B, these gases should be under a higher pressure at point A that makes them escape to the lower pressure at pint it. This is the reason why gasses escape from the pressure put on them by the walls of a balloon to outside the balloon.
Since Hemoglobin is responsible of binding with Oxygen, Carbon dioxide, and the other ligands; for gases to be exchanged at the Chorion, the Fatal Hemoglobin (a.k.a. Hemoglobin F) must be structured differently from the Adult Hemoglobin (Hemoglobin A) found in the mother’s blood in order for Oxygen molecules to have a lower partial pressure binding them with Fetal Hemoglobin than the partial pressure they have while biding with Adult Hemoglobin. And for Hemoglobin to function differently, different variants of hemoglobin that have different structures and different functions are found.
Genetics and structure of Hemoglobin Variants
Hemoglobin is a Metalloprotein, a protein that contains metal ions, the metal is Iron (Fe) in the case of hemoglobin. Hemoglobin has a quaternary biomolecular structure, in other words, Hemoglobin molecule is meanly built up from four chains of a large number of amino acids known as Protein Subunits.
In addition to the protein subunits, a Hemoglobin molecule also contains non protein compounds known as Heme (Haem) groups. Each heme group includes an Iron ion within it and is associated tightly to one of the fou protein chains that build up the Hemoglobin molecule. In other words, a quaternary structured Hemoglobin molecule contains 4 heme groups.
Due to the attraction forces inside the protein chains, they appear as a tetramer of four coils folded in order to connect together. Each of these protein chains/subunits is given a name of a Greek letter.
The difference between one Hemoglobin Variant and another comes from the type of protein subunits build up the Hemoglobin molecule. For example the Adult Hemoglobin (Hemoglobin A) molecule consists of 2 Alpha (α) protein subunits and 2 Beta (β) subunits while the Fetal Hemoglobin (Hemoglobin F) is built up from 2 alpha subunits and 2 Gamma (γ) subunits.
While the structure of a Hemoglobin Variant depends on the type of the 4 protein subunits that build up Hemoglobin molecule; the type of the protein subunit, on the other hand depends on the sequence of which the amino acids are arranged together to build the protein chain. For example the Alpha chain contains a sequence of 141 amino acids and the Beta chain contains a 146 amino acids.
The sequence of these amino acids is generated according to genetic codes located in the cell’s DNA. For example the code that defines how to generate the amino acids sequence for Alpha chains is found in a group of genes known as Alpha Globin located inside Chromosome 16 of human DNA, on the other hand, the Beta subunit is generated according to genetic code found in a group of genes known as Beta Globin located in Chromosome 11.
The “Genetics and the structure of Hemoglobin Variants” figure shows how the molecular structure of Hemoglobin Variants depends on the individual’s genes, the molecules of Hemoglobin are built up on different types of Hemoglobin Subunits which are synthesized by the cells of human body according to the genetic code found in the person’s DNA.
The figure shows three examples of Hemoglobin Subunits, the Hemoglobin Alpha (α) Chain, Hemoglobin Beta (β) Chain, and Hemoglobin Gamma (γ) Chain, the genetic code sued to generate each of these chains from a sequence of Amino Acids is located in the chromosomes 16, 11, and 11 respectively.
The figure also shows that Adult Hemoglobin (Hemoglobin A) molecule is built up from 2 Alpha chains and 2 Beta chains. The figure also shows how the molecules of Fetal Hemoglobin (Hemoglobin F) are made up from 2 Alpha Chains and 2 Gama chains. Hemoglobin Variants can be also referred to using their biomolecular structure. For example, Hemoglobin A is also known as Hemoglobin α2β2 and Hemoglobin F is known as Hemoglobin α2γ2 .
Synthesis of Hemoglobin is much more complex than what is demonstrated in the “Genetics and the structure of Hemoglobin Variants” figure, there are other components hemoglobin molecules, however, the difference between one hemoglobin variant and another comes from the difference between the subunits that build up their molecules, which a genetic difference as the figure demonstrates.
Since the type of a Hemoglobin Variant essentially depends on the individuals genes, Hemoglobin Variants are defined to be “Mutations“ of Hemoglobin. This fact also explains why disorders related to Hemoglobin Variants are classified as genetic disorders. For example, Sickle-cell Anemia, which is a genetic disorder, is caused by Hemoglobin S (α2βS2) which causes Red Blood Cells to have a Sickle shape instead of a round Shape. Hemoglobin S is a mutation of Adult Hemoglobin (α2β2), the mutation occurs as a result of replacing a single base from the genes where the genetic code sequence of Beta chains. The result will be mutated Beta chains that replaces the normal Beta chains found in Hemoglobin A molecules.