ABO blood group system
The ABO blood group system is a classification of blood types based on the presence of specific antigens on the surface of red blood cells. There are four main blood types: A, B, AB, and O, which are determined by three alleles of the ABO gene located on chromosome 9. The gene’s alleles—IA, IB, and i—interact through complete dominance and codominance to produce the observed blood types. For instance, individuals with type A blood have either the IAIA or IAi genotype, while those with type B blood are either IBIB or IBi. Type AB blood expresses both IA and IB antigens, whereas type O individuals lack these antigens altogether.
Understanding the ABO system is critical in medical settings, particularly in blood banking and transfusions, to avoid potentially fatal antigen-antibody reactions. Blood type compatibility is important; type O individuals are universal donors, while type AB individuals are universal recipients. The distribution of blood types varies across different populations, and genetic studies continue to explore potential links between blood types and health outcomes, including susceptibility to diseases like COVID-19. The ABO blood group system was first identified by Karl Landsteiner in the early 1900s, paving the way for advances in transfusion medicine and genetics.
ABO blood group system
SIGNIFICANCE: ABO blood typing has long been known to be essential for use in blood banking and for emergency transfusions. The inheritance patterns of the various ABO blood types are well understood, and the system provides a model application of various principles of classical genetics (multiple alleles, complete dominance, codominance) as applied to an important human trait.
Genetics
There are four different blood types, determined by three separate alleles of the human ABO gene. This gene is located on the long arm of chromosome 9 (9q34.2), and the three alleles are designated IA, IB, and i. There are six possible genotypes, since any one individual can only have two alleles: IAIA, IAi, IBIB, IBi, IAIB, and ii. The IA allele is completely dominant to the i allele, so individuals whose genotypes are either IAIA or IAi will have type A blood. Similarly, the IB allele is also completely dominant to the i allele, so individuals with the genotype IBIB or IBi will have type B blood. The IA and IB alleles are codominantly expressed, so the IAIB expresses a new blood type, type AB. Finally, homozygotes for the i allele, ii, exhibit O.
The ABO gene on chromosome 9 contains seven exons (coding regions) and is spread out over eighteen thousand bases of DNA. There is a deletion of a single guanine base in exon 6 that distinguishes the i allele from the IA allele. At seven separate locations within this long gene are single nucleotide substitutions that distinguish the IA and the IB alleles. The protein product of the ABO gene is a glycosyltransferase enzyme that determines the specific carbohydrate structures that will be added on to certain surface proteins on red blood cells.
Immunology and Blood Banking
The IA and IB alleles specify two different functional glycosyltransferases that modify the surface proteins on red blood cells in slightly different ways. Each of these modifications is antigenic, since it can provoke an antibody response in some individuals. Type A individuals produce the A antigen, while type B individuals produce the B antigen. Type AB individuals produce and express both the A and the B antigens. Type O individuals produce a nonfunctional glycosyltransferase that does not modify the surface proteins at all, so neither the A nor the B antigen is present. Lacking the A and B antigens, type O individuals will produce antibodies directed against these antigens when exposed to them. Similarly, type A individuals will produce anti-B antibodies, while people with blood type B will produce anti-A antibodies. Type AB individuals do not produce either anti-A or anti-B antibodies.
In blood banks and in cases of blood transfusions, it is essential to avoid antigen-antibody reactions, since such reactions kill and agglutinate red blood cells and can cause death to the patient. Blood type compatibility with regard to donor and recipient can thus be summarized as follows: Type O individuals (universal donors) can donate blood to a patient with any of the four blood types, since the red blood cells of type O do not contain any surface antigens that would provoke the reaction. However, they can only receive blood from other type O individuals. Type AB individuals (universal recipients) can receive blood from people with any of the four blood types, since they produce neither the anti-A nor the anti-B antibodies. However, they can give blood only to other type AB recipients. People with blood type A can give to A and AB recipients only and can receive from types A and O only. Similarly, type B individuals can give only to B and AB and receive only from B and O.
Population Data
The distribution of the four blood groups and the associated allele frequencies varies considerably among different populations around the world. A survey of blood donations in the United States between 1991 and 2000 found that approximately 46.6 percent of the US population was type O, 37.1 percent was type A, 12.2 percent was type B, and 4.1 percent was type AB. The frequency of the IB allele is highest among central Asian populations, where it can reach over 30 percent, while the i allele is found with greater than 90 percent frequency among native South American peoples.
In the 2020s, researchers were conducting studies to see if there was a link between blood type and the progression and prognosis of COVID-19. Although more research was needed, their studies suggested that people with type A were more susceptible to the virus than others.
Paternity Testing
For many years starting in the 1920s, blood typing was used as a legal defense in cases where a man was being sued for paternity. In some cases, the demonstration of a particular blood type in the male defendant could exclude the possibility that he was the father of the child in question. For example, if the mother were type A and her child were type O, the father could not be type AB. Since the child has the genotype ii, its father cannot have the genotype IAIB; he would have to have at least one i allele.
One infamous trial of this sort occurred in 1943, when the famous silent-film actor Charlie Chaplin was named in a paternity suit by Joan Barry. Barry was shown to have type A blood, while her child was type B (genotype IBi). Clearly the father must have been either type B or type AB in order to have contributed the IB allele to the child. Chaplin had type O blood, yet he was convicted and made to pay a substantial amount in child support. In subsequent years, as lawyers and judges came to better understand genetic evidence of this sort, such miscarriages of justice were rare.
It is important to note that blood typing evidence by itself is never enough to prove that a particular individual is the father, but it may be sufficient to rule out paternity. DNA fingerprinting, a much more sensitive and involved molecular analysis, can now be used to determine paternity with a high degree of certainty.
Impact
The Austrian scientist Karl Landsteiner was the first to discover the ABO blood groups. In 1900, he noted that red blood cells of some individuals could be agglutinated by the blood serum from other individuals; the following year, he published a paper in which he identified three different blood groups: A, B, and C (later O). Landsteiner was recognized for his work in 1930, when he was awarded the Nobel Prize in Physiology or Medicine.
The elucidation of the workings of the ABO blood group system was the first of several significant discoveries that made it possible to develop safe procedures for blood transfusion. The ABO system has been a model for basic research in immunology to understand the complexities of antigen-antibody recognition and binding. Since the successful cloning of the human ABO gene in 1990 and the completion of the Human Genome Project in 2003, great progress has been made in understanding the structure-function relationships between the ABO alleles and the glycosyltransferases they encode.
Key Terms
- alleleone of two or more alternative forms of a gene
- antibodya protein produced by the immune system that recognizes a foreign substance (antigen) and binds to it, targeting it for destruction
- antigena foreign molecule that is recognized by a particular antibody
- codominancewhen the two alleles are both expressed in a heterozygote; neither is dominant over the other
- complete dominancewhen a single allele determines the phenotype in a heterozygote; the dominant allele is expressed, while the recessive allele is masked
- glycosyltransferasean enzyme that catalyzes the transfer of a sugar group from one molecule to another
- heterozygotean individual who has two different alleles of a particular gene
- homozygotean individual who has two identical copies of the same allele
Bibliography
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