How many alleles are there for the four main types of human blood? one two three four

The A and B antigen molecules on the surface of red blood cells are made by two different enzymes. These two enzymes are encoded by different versions, or alleles, of the same gene.

The A allele codes for an enzyme that makes the A antigen, and the B allele codes for an enzyme that makes the B antigen. A third version of this gene, the O allele, codes for a protein that is not functional; it makes no surface molecules at all.

Everyone inherits two alleles of the gene, one from each parent. The combination of your two alleles determines your blood type.

The table on the left shows all of the possible combinations of blood type alleles. The blood type for each allele combination is shown on the right. For example, if you inherit a B allele from your father and an A allele from your mother, your blood type will be AB.

Our blood is composed of blood cells and an aqueous fluid known as plasma. Human blood type is determined by the presence or absence of certain identifiers on the surface of red blood cells. These identifiers, also called antigens, help the body's immune system to recognize its own red blood cell type.

There are four main ABO blood type groupings: A, B, AB, and O. These blood groups are determined by the antigen on the blood cell surface and the antibodies present in the blood plasma. Antibodies (also called immunoglobulins) are specialized proteins that identify and defend against foreign intruders to the body. Antibodies recognize and bind to specific antigens so that the foreign substance can be destroyed.

Antibodies in an individual's blood plasma will be different from the antigen type present on the red blood cell surface. For example, a person with type A blood will have A antigens on the blood cell membrane and type B antibodies (anti-B) in the blood plasma.

ABO blood group antigens present on red blood cells and IgM antibodies present in the serum. InvictaHOG/Wikimedia Commons/Public Domain Image

While the genes for most human traits exist in two alternative forms or alleles, the genes that determine human ABO blood types exist as three alleles (A, B, O). These multiple alleles are passed from parent to offspring such that one allele is inherited from each parent. There are six possible genotypes (genetic makeup of inherited alleles) and four phenotypes (expressed physical trait) for human ABO blood types. The A and B alleles are dominant to the O allele. When both inherited alleles are O, the genotype is homozygous recessive and the blood type is O. When one of the inherited alleles is A and the other is B, the genotype is heterozygous and the blood type is AB. AB blood type is an example of co-dominance since both traits are expressed equally.

• Type A: The genotype is either AA or AO. The antigens on the blood cell are A and the antibodies in the blood plasma are B.
• Type B: The genotype is either BB or BO. The antigens on the blood cell are B and the antibodies in the blood plasma are A.
• Type AB: The genotype is AB. The antigens on the blood cell are A and B. There are no A or B antibodies in the blood plasma.
• Type O: The genotype is OO. There are no A or B antigens on the blood cell. The antibodies in the blood plasma are A and B.

Due to the fact that a person with one blood type produces antibodies against another blood type when exposed to it, it is important that individuals be given compatible blood types for transfusions. For example, a person with blood type B makes antibodies against blood type A. If this person is given blood of type A, his or her type A antibodies will bind to the antigens on the type A blood cells and initiate a cascade of events that will cause the blood to clump together. This can be deadly as the clumped cells can block blood vessels and prevent proper blood flow in the cardiovascular system. Since people with type AB blood have no A or B antibodies in their blood plasma, they can receive blood from persons with A, B, AB, or O type blood.

Blood Group Test. MAURO FERMARIELLO/Science Photo Library/Getty Images

In addition to the ABO group antigens, there is another blood group antigen located on red blood cell surfaces. Known as the Rhesus factor or Rh factor, this antigen may be present or absent from red blood cells. Studies performed with the rhesus monkey lead to the discovery of this factor, hence the name Rh factor.

Rh Positive or Rh Negative: If the Rh factor is present on the blood cell surface, the blood type is said to be Rh positive (Rh+). If absent, the blood type is Rh negative (Rh-). A person who is Rh- will produce antibodies against Rh+ blood cells if exposed to them. A person can become exposed to Rh+ blood in instances such as a blood transfusion or a pregnancy where the Rh- mother has an Rh+ child. In the case of an Rh- mother and Rh+ fetus, exposure to the blood of the fetus can cause the mother to build up antibodies against the child's blood. This can result in hemolytic disease in which fetal red blood cells are destroyed by antibodies from the mother. To prevent this from happening, Rh- mothers are given Rhogam injections to stop the development of antibodies against the blood of the fetus. Like the ABO antigens, the Rh factor is also an inherited trait with possible genotypes of Rh+ (Rh+/Rh+ or Rh+/Rh-) and Rh- (Rh-/Rh-). A person who is Rh+ can receive blood from someone who is Rh+ or Rh- without any negative consequences. However, a person who is Rh- should only receive blood from someone who is Rh-.

Blood Type Combinations: Combining the ABO and Rh factor blood groups, there are a total of eight possible blood types. These types are A+, A-, B+, B-, AB+, AB-, O+, and O-. Individuals who are AB+ are called universal recipients because they can receive any blood type. Persons who are O- are called universal donors because they can donate blood to persons with any blood type.

The four basic ABO phenotypes are O, A, B, and AB. After it was found that blood group A RBCs reacted differently to a particular antibody (later called anti-A1), the blood group was divided into two phenotypes, A1 and A2. RBCs with the A1 phenotype react with anti-A1 and make up about 80% of blood type A. RBCs with the A2 phenotype do not react with anti-A1 and they make up about 20% of blood type A. A1 red cells express about 5 times more A antigen than A2 red cells, but both types of red cell react with anti-A, and as far as transfusion purposes are concerned, the A1 and A2 blood groups are interchangeable.

There are many other subgroups of blood group A in which RBCs tend to weakly express the A antigen, whereas weak variants of the blood group B phenotype are rare (2).

The immune system forms antibodies against whichever ABO blood group antigens are not found on the individual's RBCs. Thus, a group A individual will have anti-B antibodies and a group B individual will have anti-A antibodies. Blood group O is common, and individuals with this blood type will have both anti-A and anti-B in their serum. Blood group AB is the least common, and these individuals will have neither anti-A nor anti-B in their serum.

ABO antibodies in the serum are formed naturally. Their production is stimulated when the immune system encounters the "missing" ABO blood group antigens in foods or in micro-organisms. This happens at an early age because sugars that are identical to, or very similar to, the ABO blood group antigens are found throughout nature.

The ABO locus has three main alleleic forms: A, B, and O. The A allele encodes a glycosyltransferase that produces the A antigen (N-acetylgalactosamine is its immunodominant sugar), and the B allele encodes a glycosyltransferase that creates the B antigen (D-galactose is its immunodominant sugar).

See the structures of the A, B, and O antigens in Stryer's Biochemistry

The O allele encodes an enzyme with no function, and therefore neither A or B antigen is produced, leaving the underlying precursor (the H antigen) unchanged. These antigens are incorporated into one of four types of oligosaccharide chain, type 2 being the most common in the antigen-carrying molecules in RBC membranes. Some of the other enzymes involved in the earlier stages of ABO antigen synthesis are also involved in producing antigens of the Hh blood group and the Lewis blood group.

Although the ABO blood group antigens are regarded as RBC antigens, they are actually expressed on a wide variety of human tissues and are present on most epithelial and endothelial cells.

Each human RBC expresses about 2 million ABO blood group antigens. Other blood cells, such as T cells, B cells, and platelets, have ABO blood group antigens that have been adsorbed from the plasma. In individuals who are "secretors", a soluble form of the ABO blood group antigens is found in saliva and in all bodily fluids except for the cerebrospinal fluid.

A number of illnesses may alter a person's ABO phenotype. Patients can "acquire" the B antigen during a necrotizing infection during which bacteria release an enzyme into the circulation that converts the A1 antigen into a B-like antigen (3). During this time, patients should not receive blood products that contain the B antigen because their sera will still contain anti-B. Once the underlying infection is treated, the patients' blood groups return to normal.

Illness can also cause patients to "lose" ABO blood group antigens. Any disease that increases the body's demand for RBCs may weaken the expression of ABO blood group antigens, e.g., thalassemia. In addition, ABO blood group antigens can be altered by hematological cancers that can modify the sugar chains that bear the ABO blood group antigens, lending to the use of the A and B antigens as tumor markers for acute leukemia, myeloproliferative disorders, and myelodysplasia.

The functions of the ABO blood group antigens are not known. Individuals who lack the A and B antigens are healthy, suggesting that any function the antigens have is not important, at least not in modern times.

No diseases are known to result from the lack of expression of ABO blood group antigens, but the susceptibility to a number of diseases has been linked with a person's ABO phenotype. Such correlations remain controversial and include the observation that gastric cancer appears to be more common in group A individuals (4), whereas gastric and duodenal ulcers occur more often in group O individuals (5).

A clear correlation has been established between the ABO phenotype and the level of two proteins involved in blood clotting; factor VII (FVIII) and von Willebrand factor (vWF) (6). Blood group O individuals have about 25% less FVIII and vWF in their plasma. It is well established that low levels of FVIII and vWF are a cause of excess bleeding, and therefore it may also be the case that increased levels make clotting more likely, increasing the risk of both arterial (ischemic heart disease) and venous (thromboembolic disease) problems. Indeed, non-group O individuals have been shown to be at an increased risk of both arterial and venous disease (6).