The Colton blood group system, despite the knowledge known about its genetics and
biochemistry, has remained a relatively uncomplicated system. In 1967, Heisto et al.
reported three examples of a similar antibody against a high frequency antigen they named
Coa (Colton) after one of the antibody producers.
(Unfortunately, like the Lutheran blood group system, the authors misread the name of the
individual chosen, as the original individual's name was in-fact Calton). Giles et
al., in 1970, identified the antithetical antibody, anti-Cob,
and the blood group system was established. Coa is present on
the red cells in 99.9 % of most populations, with a slightly lower incidence in Northern
Europeans. Alternatively, Cob is present in 8 to 10 % of
Northern Europeans with much lower incidence in other populations. The Co (a-b-)
phenotype, the anticipated "null" phenotype, was reported by Rogers et al. in
1974 and Conull cells have reduced water permeability. This made
the system somewhat similar to other systems known at that time in that the "null phenotype"
individual had produced an antibody of a single specificity that reacted with cells of all
Colton phenotypes except Co (a-b-). Thus, this indicated a third antigen, Co3, present on
all cells having either Colton allele. Moulds et al. (1973) and Swanson et al. (1978) had
reported the possibility of a rare silent allele from separate family studies.
Antibodies to the Colton antigens have caused both mild and moderate hemolytic
transfusion reactions and mild hemolytic disease of the newborn, except in one severe case
due to anti-Co3. In this case the antibody titer was greater than 32,000 and the baby was
supported by intrauterine and post-delivery maternal transfusions.
As a blood group system, Colton had been of limited clinical interest except for
suggestions of linkage with monosomy 7, weaker expression with certain chromosomal 7
rearrangements and congenital dyserythropoietic anemia. Then, through a series of
excellent studies by Agre et al. (1991), Smith et al. (1994) and Preston et al. (1994),
Colton antigens were found to be located on the channel forming integral protein (CHIP-1).
CHIP-1 is a product of the AQPI (Aquaporin-1) gene located on the short arm
of chromosome 7 at 7p14. This 269 amino acid membrane glycoprotein has six a -helices forming a trapezoid-like cylinder. There is a
branched rod-like structure within the cylinder that transverses the membrane and likely
contains a least one a -helix. The function of
this protein is essentially a regulated water channel through the membrane. An amino acid
change of Ala45 to Val45 represents
the difference between Coa and Cob,
respectively. The location of Co3 on CHIP-1 is unknown.
Investigation of blood from three unrelated Co (a-b-) individuals revealed that the
serological aberration was due to three separate causes: a frame shift after Gly104,
a deletion of exon 1 and a Leu38 (instead of a Pro38)
causing a stop. These three individuals lacked or had a very low amount of CHIP-1. The
CHIP-1 protein (hence the Colton blood group antigens) is located on a variety of surfaces
including epithelia, endothelium, descending tubules and apical surfaces of proximal
tubules in addition to red blood cells. However, the Co(a-b-) individuals do not appear to
have any health related problems related to the loss of this protein.