Inheritance

Alleles

The ABO system is controlled by 3 alleles (A, B, and O ), any one of which can occupy the ABO locus. People inherit one of these alleles from each parent. The A and B genes are codominant, and the O gene is a silent gene or amorph which does not produce an antigen. The ABO locus is on chromosome #9.

The ABO system is also controlled by two other genes, H and h, which are inherited at an independent locus. The h gene can be thought of as an amorph, or as a recessive gene, and it is extremely rare. Almost everyone inherits two H genes. The H gene makes H antigen, and both A and B antigens use H antigen as a substrate.

Genetic Pathway

ABO inheritance must be explained by way of a genetic pathway because ABH antigens are indirect gene products. They result from genes that produce enzymes known as transferases. Transferases pick up sugars from carrier molecules and attach them to receptor molecules. These terminal sugars are responsible of ABH antigen specificity (Figure 4-1). The basic structure of ABH antigens (Figure 4-2) and their genetic pathways (Figure 4-3) are described below.

If an H gene is inherited:

Precursor substance (P.S.) + H gene converts P.S. to H antigen (L-fucose).
NOTE: "Converts" means the H gene makes a transferase called L-fucosyl transferase which adds L-fucose to both type 1 and type 2 chains of the P.S. With L-fucose as a terminal sugar, P.S. becomes H antigen.

If only O genes are inherited:

H antigen + O genes (amorph) ---> no change. Therefore, the only antigen on group O cells is H antigen.

If an A gene is inherited:

H antigen + A gene ---> converts H to A antigen (N-acetyl-D-galactosamine).

The A gene makes N-acetyl-D-galactosaminyl transferase which adds N-acetyl-D-galactosamine (GALNac) to the sugar chain with a terminal H antigen. Once GALNac is added, H antigen becomes A antigen. However, not all of the H antigen is converted into A antigen. Therefore, group A red cells have both A and H antigens.

If a B gene is inherited:

H antigen + B gene ---> converts H to B antigen (D-galactose).

The B gene makes D-galactosyl transferase which adds D-galactose to the sugar chain with a terminal H antigen. Because not all H antigens are converted to B antigens, group B cells have both B and H antigens.

If both A and B genes are inherited:

Inheritance