The ABO blood group system is one of the best-understood examples of multiple alleles, codominance, and dominance relationships in human genetics. Three alleles (multiple alleles) of a single gene (I gene, located on chromosome 9) determine ABO blood type: IA allele: encodes glycosyltransferase enzyme that adds N-acetylgalactosamine to the H antigen on red blood cells, creating the A antigen. IB allele: encodes glycosyltransferase enzyme that adds galactose to the H antigen, creating the B antigen. i (or IO) allele: encodes a non-functional enzyme; no specific antigen is added to the H antigen (which remains as the O antigen). Dominance relationships: IA and IB are codominant to each other (both are fully expressed simultaneously when present together in IAIB individuals, producing both A and B antigens). Both IA and IB are dominant over i (one copy of IA or IB is sufficient to produce detectable A or B antigen respectively, so IAi = type A and IBi = type B). The i allele is fully recessive — ii individuals produce neither A nor B antigens and are blood type O.

Understanding blood type inheritance requires correctly identifying the genotype (or possible genotypes) of each parent and then determining which allele combinations are possible in offspring. For ABO blood typing crosses, the key rules are: IAIA (type A): donates only IA. IAi (type A): donates IA or i (50:50). IBIB (type B): donates only IB. IBi (type B): donates IB or i (50:50). IAIB (type AB): donates IA or IB (50:50) — critically, this person has NO i allele to donate. ii (type O): donates only i. For blood group O (ii) to appear among offspring, BOTH parents must carry at least one i allele — since ii requires one i from each parent, any parent who does not carry an i allele (specifically, type AB individuals with genotype IAIB) absolutely cannot contribute to producing a type O offspring, regardless of the other parent's genotype. This makes crosses involving one IAIB parent diagnostically important: they can NEVER produce type O children.

The ABO blood group system beautifully illustrates two important genetic concepts that extend beyond simple Mendelian dominance: Multiple alleles: while each individual can carry at most two alleles of any gene (one per homologous chromosome), a gene can exist in more than two allelic forms in the population. The I gene has three common alleles (IA, IB, and i) in the human population, allowing six possible genotypes (IAIA, IAi, IBIB, IBi, IAIB, ii) and four blood types. Multiple alleles arise through different mutations in the same gene, each producing a slightly different or non-functional protein product. Codominance: in IAIB individuals, both the IA and IB alleles are fully and simultaneously expressed — red blood cells display both A and B antigens on their surfaces, and neither allele suppresses the other's expression. This contrasts with complete dominance (where the dominant allele's product is expressed and the recessive allele's product is not) and incomplete dominance (where the heterozygote shows an intermediate phenotype). Codominance occurs when both alleles produce a detectable, independently functional product — in this case, two different glycosyltransferase enzymes that both function simultaneously to produce two different antigens, each detectable using specific antibodies.

Understanding ABO blood group genetics is critically important in clinical medicine, particularly for blood transfusion and organ transplantation. Blood transfusion compatibility: transfusion of ABO-incompatible blood can cause a severe, potentially fatal acute haemolytic transfusion reaction, in which the recipient's pre-formed anti-A and/or anti-B antibodies (IgM and IgG) bind to donor red blood cell antigens, activating complement, causing rapid intravascular haemolysis (destruction of donor RBCs within blood vessels), haemoglobinaemia, and potentially acute kidney injury, disseminated intravascular coagulation (DIC), and circulatory collapse. Blood type O− individuals are sometimes called "universal donors" (their red cells lack both A and B antigens and the Rh D antigen, making them compatible with recipients of all ABO and Rh types), though in modern blood banking practice, crossmatching and type-specific blood is always preferred when time permits. Blood type AB+ individuals are "universal recipients" (their plasma lacks anti-A and anti-B antibodies, so they can receive red blood cells of any ABO type, and they are also Rh+). Organ transplantation: ABO compatibility is required for solid organ transplants (kidney, heart, liver) to prevent immediate antibody-mediated rejection; ABO-incompatible transplants are possible under specific protocols involving pre-transplant antibody removal and immunosuppression but are considerably more complex.