Blood Type ABO and More

The ABO blood type was discovered by Austrian-American biologist Karl Landsteiner in 1900, who was awarded the Nobel Prize in 1930. Even today the major components in kits used to identify blood type are the same antiserums (anti-A and anti-B) that Landsteiner used over a century ago. If a given antiserum reacts with a tiny drop of your blood and agglutinates, it means you are positive for that blood type. A visual representation of four blood types is shown below.

Since it was first performed in 1907, ABO blood typing has become the most important phenotypic test in finding compatible blood donors and recipients. The following chart summarizes all possible donor-recipient scenarios:

When gene theory is applied to the observed inheritance pattern of ABO blood types, it is apparent that the blood type is determined by a single gene locus with three different alleles (An allele is an alternative form of a gene) which we will refer to as the A, B and O alleles. Since a normal individual has two copies of each gene, one from their father and one from their mother, he or she has six different possible genotypes: AA, AB, AO, BB, BO and OO. Among the three alleles, O is recessive to A and B, which means  a phenotypic O only occurs when both of your alleles are O; otherwise you will be either A or B. However, allele A and B are co-dominant, which means that an AB genotype gives rise to AB phenotype. A summary of this inheritance rule is as follows:

The complete picture about the ABO genotype and phenotype determination was finally revealed when the gene of ABO locus was identified in 1990. The gene in question encodes for a protein called glycosyltransferase, an enzyme that acts as a catalyst for the transfer of a monosaccharide unit from an activated nucleotide sugar (also known as the "glycosyl donor") to a glycosyl acceptor molecule. Although there is no conclusive evidence as to which of the three alleles was the evolutionary origin, it is clear that they act differently on the acceptor molecule.   At the DNA level, the A and O allele are identical with the exception of a single base pair missing from O. Because of this deletion, the O-allele product is a defective enzyme that does not modify the acceptor at all. The A and B alleles differ by seven nucleotides (substitutions), four of which translate into different amino acids. Because of these substitutions, the A allele encodes a glycosyltransferase that bonds α-N-acetylgalactosamine to the acceptor, while the B allele encodes an enzyme joins α-D-galactose to the acceptor. The acceptor being a cell surface molecule on the red blood cells, called the H antigen. This explains agglutination we observe during blood tests as mentioned above:  the antibodies in the antiserum recognize the cell surface antigen from incompatible blood type and lyses the red blood cells.

It is interesting to note that the distribution of blood type is different between countries and within different ethnic groups (see the chart below as an example). The general trend is that Type-O is the most frequent, followed by A and then B with type AB as the least common. If you sample the genotypes of any given population, you will find that the frequency of the three alleles of the ABO gene matches the observed phenotypes.

Knowing the exact genotypes that give rise to different phenotypes (ABO blood types) would make it easier to understand why people with certain blood type are more susceptible to certain diseases. First of all, it’s important to point out that Glycosyltransferase, the ABO gene product, exists in many other types of cells in our body and that the H-antigen is not the only acceptor of its target. One such acceptor is called the von Willebrand factor (vWF). The glyconized vWF has a longer half-life than the un-modified vWF (25 hours versus 10 hours). Evidence seems to suggest that a higher level of vWF in the blood raises the likelihood of blood clot formation. Therefore, in non-O blood type populations, there is a greater susceptibility for arterial and venous thromboembolism (VTE).

Based on the genetic background of ABO blood types we can see how genetic variants of an enzyme can lead to different blood types and disease susceptibility.   Knowing and understanding a little about genetics can be the key to understanding yourself, your body, and your health.