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So You Think You Know the Types of Hemoglobin in Humans? Read This

Types of Hemoglobin in Humans
Hemoglobin is the primary protein responsible for oxygen transport in vertebrates. In humans, different types of hemoglobin molecules are synthesized during the embryonic, fetal and adult stages.
Bodytomy Staff
Last Updated: Apr 25, 2018
Did You Know?
The type and concentration of hemoglobin molecules influences the shape of red blood cells as well as the viscosity of blood.
Hemoglobin is a type of respiratory protein present in the red blood cells or erythrocytes, and is involved in the transportation of oxygen from lungs to all the different tissues of the body.

Hemoglobin is a globular protein made up of four subunits called globins, each of which contains a polypeptide chain bound to a heme group. The globins comprise a set of amino acids that form helical structures joined by non-helical segments.
Different types of globins are synthesized and bound together to form the hemoglobin molecule in different stages of development. The resulting types of hemoglobin have been explained below, in order of the developmental stages.
Types of Hemoglobin
Each hemoglobin macromolecule is made up of 2 pairs of globins. Six different types of globins, namely α, β, γ, δ, ε, and ζ are produced in a stage-dependent manner.
Of these, the genes for ζ and α globins are present on chromosome 16, whereas those for the rest of the globins are located on chromosome 11. 2 identical globins synthesized from chromosome 11 pair with 2 identical globins synthesized from chromosome 16 to form a total of 8 different types of hemoglobin.
Embryo
Human Embryo
The existence of a different type of hemoglobin in human embryos was first described by Huehns et al in 1964. Although embryonic hemoglobin is relatively less studied due to the lack of availability of suitable samples, four different types have been identified. These are:

Gower 1: 2 ζ and 2 ε
Gower 2: 2 α and 2 ε
Portland I: 2 ζ and 2 γ
Portland II: 2 ζ and 2 β
The Gower 1 and 2 are synthesized by erythroid cells in the embryonic yolk sac, and are predominant till the eighth week from fertilization.
Fetus
Human Fetus
From the ninth week since conception, the embryonic stage ends and the fetal stage commences. The embryonic hemoglobin molecules are gradually replaced by fetal hemoglobin or HbF, which is composed of two α and two γ globins.

At birth, about 50 - 80% of the hemoglobin comprises fetal hemoglobin, and its level gradually declines after birth. By the end of six moths, it reduces to about 8% of the total hemoglobin content.
The maternal blood that is supplied to the developing fetus is lower in oxygen than the blood present in normal arterioles. Hence, the fetal hemoglobin has a higher affinity for oxygen as compared to adult hemoglobin. The presence of γ globin chains instead of the β globins of adult hemoglobin is one of the ways to achieve such higher affinity.
Adults
From the sixth month of growth, the synthesis of fetal hemoglobin declines, and that of adult hemoglobin increases. The two main types of hemoglobin found in adults are:

A: 2 α and 2 β
A2: 2 ζ and 2 δ
In adults, fetal hemoglobin is also synthesized, but only in a specialized set of RBCs called F-cells that are present in the pancreas. These F-cells make up about 3 - 7% of the total RBCs in adults, and the resulting HbF comprises 0.8 - 2% of the total hemoglobin molecules.
From the age of six months, HbA is the predominant type of hemoglobin in humans and accounts for 95 - 98% of the total hemoglobin molecules. HbA2, on the other hand, exists in small amounts and makes up 2 - 3% of the total hemoglobin molecules in adults.
Abnormal Types and Variants
More than 750 variants of the hemoglobin molecule have been identified till today. Several variants are the result of a single mutation in one of the globin genes.
The resultant abnormal hemoglobin molecules give rise to a range of disorders which are broadly grouped as Alpha-thalassemias (α-thalassemias) and Beta-thalassemias (β-thalassemias). In addition to these, sickle-cell anemia (SCA) is a disease that involves a specific mutation in the β globin gene, that ultimately distorts RBCs making them sickle-shaped.
Some of the abnormal variants have been listed below, along with the globin chain affected and the resulting disease.

Disease Hemoglobin Type
Alpha-thalassemias (Mutation in α globin) H (β4)
Barts (γ4)
Beta-thalassemias (Mutation in β globin) C (α2βC2)
E (α2βE2)
D (α2βD2)
Sickle cell disease (Mutation in β globin) S (α2βS2)
Note: The above-mentioned diseases are inherited in an autosomal recessive manner. It means that the disease gets manifested only when two copies of the defective gene are inherited. If one of the inherited genes is normal, the individual may remain asymptomatic.
The blood test used to identify the different types of hemoglobin molecules present in blood is termed as hemoglobin electrophoresis. Here, the protein molecules separate out with respect to their size, under the influence of electric field. This test helps to identify the presence of abnormal hemoglobin types (if any) and aid the diagnosis of hemoglobin disorders.