Hemoglobinopathy
Encyclopedia
Hemoglobinopathy is a kind of gene
tic defect that results in abnormal structure of one of the globin
chains of the hemoglobin
molecule. Hemoglobinopathies are inherited single-gene disorders; in most cases, they are inherited as autosomal co-dominant traits. Common hemoglobinopathies include sickle-cell disease
. It is estimated that 7% of worlds population (420 million) are carriers, with 60% of total and 70% pathological being in Africa. Hemoglobinopathies are most common in ethnic populations from Africa, the Mediterranean basin and Southeast Asia.
Hemoglobinopathies imply structural abnormalities in the globin proteins themselves. Thalassemia
s, in contrast, usually result in underproduction of normal globin protein
s, often through mutations in regulatory genes. The two conditions may overlap, however, since some conditions which cause abnormalities in globin proteins (hemoglobinopathy) also affect their production (thalassemia). Thus, some hemoglobinopathies are also thalassemias, but most are not.
Either hemoglobinopathy or thalassemia, or both, may cause anemia. Some well-known hemoglobin variants such as sickle-cell anemia and congenital dyserythropoietic anemia
are responsible for diseases, and are considered hemoglobinopathies. However, many hemoglobin variants
do not cause pathology or anemia, and thus are often not classed as hemoglobinopathies, because they are not considered pathologies. Hemoglobin variants
are a part of the normal embryonic and fetal development, but may also be pathologic mutant forms of hemoglobin in a population
, caused by variations in genetics. Other variants cause no detectable pathology
, and are thus considered non-pathological variants.
In general a sickling test (sodium bisulfite) is performed on abnormal hemoglobins migrating in the S location to see if the red cells precipitate in solution.
This is how abnormal hemoglobin variants are isolated and identified using these two methods. For example a Hgb G-Philadelphia would migrate with S on alkaline electrophoresis and would migrate with A on acid electrophoresis, respectively.
) seem to have given an evolutionary benefit, especially to heterozygotes, in areas where malaria
is endemic. Malaria parasites live inside red blood cells, but subtly disturb normal cellular function. In patients predisposed for rapid clearance of red blood cells, this may lead to early destruction of cells infected with the parasite and increased chance of survival for the carrier of the trait.
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
tic defect that results in abnormal structure of one of the globin
Globin
Globins are a related family of proteins, which are thought to share a common ancestor. These proteins all incorporate the globin fold, a series of eight alpha helical segments. Two prominent members of this family include myoglobin and hemoglobin, which both bind the heme prosthetic group...
chains of the hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
molecule. Hemoglobinopathies are inherited single-gene disorders; in most cases, they are inherited as autosomal co-dominant traits. Common hemoglobinopathies include sickle-cell disease
Sickle-cell disease
Sickle-cell disease , or sickle-cell anaemia or drepanocytosis, is an autosomal recessive genetic blood disorder with overdominance, characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various...
. It is estimated that 7% of worlds population (420 million) are carriers, with 60% of total and 70% pathological being in Africa. Hemoglobinopathies are most common in ethnic populations from Africa, the Mediterranean basin and Southeast Asia.
Hemoglobinopathies imply structural abnormalities in the globin proteins themselves. Thalassemia
Thalassemia
Thalassemia is an inherited autosomal recessive blood disease that originated in the Mediterranean region. In thalassemia the genetic defect, which could be either mutation or deletion, results in reduced rate of synthesis or no synthesis of one of the globin chains that make up hemoglobin...
s, in contrast, usually result in underproduction of normal globin protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s, often through mutations in regulatory genes. The two conditions may overlap, however, since some conditions which cause abnormalities in globin proteins (hemoglobinopathy) also affect their production (thalassemia). Thus, some hemoglobinopathies are also thalassemias, but most are not.
Either hemoglobinopathy or thalassemia, or both, may cause anemia. Some well-known hemoglobin variants such as sickle-cell anemia and congenital dyserythropoietic anemia
Congenital dyserythropoietic anemia
Congenital dyserythropoietic anemia is a rare blood disorder, similar to the thalassemias. CDA is one of many types of anemia, characterized by ineffective erythropoiesis, and resulting from a decrease in the number of red blood cells in the body and a less than normal quantity of hemoglobin in...
are responsible for diseases, and are considered hemoglobinopathies. However, many hemoglobin variants
Hemoglobin variants
Hemoglobin variants are mutant forms of hemoglobin in a population , caused by variations in genetics. Some well-known hemoglobin variants such as sickle-cell anemia are responsible for diseases, and are considered hemoglobinopathies...
do not cause pathology or anemia, and thus are often not classed as hemoglobinopathies, because they are not considered pathologies. Hemoglobin variants
Hemoglobin variants
Hemoglobin variants are mutant forms of hemoglobin in a population , caused by variations in genetics. Some well-known hemoglobin variants such as sickle-cell anemia are responsible for diseases, and are considered hemoglobinopathies...
are a part of the normal embryonic and fetal development, but may also be pathologic mutant forms of hemoglobin in a population
Population
A population is all the organisms that both belong to the same group or species and live in the same geographical area. The area that is used to define a sexual population is such that inter-breeding is possible between any pair within the area and more probable than cross-breeding with individuals...
, caused by variations in genetics. Other variants cause no detectable pathology
Pathology
Pathology is the precise study and diagnosis of disease. The word pathology is from Ancient Greek , pathos, "feeling, suffering"; and , -logia, "the study of". Pathologization, to pathologize, refers to the process of defining a condition or behavior as pathological, e.g. pathological gambling....
, and are thus considered non-pathological variants.
Migration patterns (Alkaline Electrophoresis)
In general on alkaline electrophoresis in order of increasing mobility are hemoglobins A2, E=O=C, G=D=S=Lepore, F, A, K, J, Bart's, N, I, and H.In general a sickling test (sodium bisulfite) is performed on abnormal hemoglobins migrating in the S location to see if the red cells precipitate in solution.
Migration patterns (Acid Electrophoresis)
In general on acid electrophoresis in order of increasing mobility are hemoglobins F, A=D=G=E=O=Lepore, S, and C.This is how abnormal hemoglobin variants are isolated and identified using these two methods. For example a Hgb G-Philadelphia would migrate with S on alkaline electrophoresis and would migrate with A on acid electrophoresis, respectively.
Hemoglobin Variants
- Hb S
- Hb CHemoglobin CHemoglobin C is an abnormal hemoglobin with substitution of a lysine residue for a glutamic acid residue at the 6th position of the β-globin chain.-Clinical significance:...
- Hb E
- Hb D-Punjab
- Hb O-Arab
- Hb G-Philadelphia
- Hb Hasharon
- Hb Korle-Bu
- Hb Lepore
- Hb M
- Hb Kansas (β102 Asn>Thr)
Hemoglobinopathy and evolution
Some hemoglobinopathies (and also related diseases like glucose-6-phosphate dehydrogenase deficiencyGlucose-6-phosphate dehydrogenase deficiency
Glucose-6-phosphate dehydrogenase deficiency is an X-linked recessive hereditary disease characterised by abnormally low levels of glucose-6-phosphate dehydrogenase , a metabolic enzyme involved in the pentose phosphate pathway, especially important in red blood cell metabolism. G6PD deficiency is...
) seem to have given an evolutionary benefit, especially to heterozygotes, in areas where malaria
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by eukaryotic protists of the genus Plasmodium. The disease results from the multiplication of Plasmodium parasites within red blood cells, causing symptoms that typically include fever and headache, in severe cases...
is endemic. Malaria parasites live inside red blood cells, but subtly disturb normal cellular function. In patients predisposed for rapid clearance of red blood cells, this may lead to early destruction of cells infected with the parasite and increased chance of survival for the carrier of the trait.