Antigen Expression - Variation in Antigen Expression

        RBCs from individuals who are homozygous for an allele typically have a greater number of antigen sites than do individuals who are heterozygous. Consequently, their RBCs can react more strongly with antibody. This difference in expression and antigen–antibody reactivity because of zygosity is known as dosage. For example, RBCs from a homozygous MM individual carry a double dose of M antigen and react more strongly with anti-M than do RBCs from a MN heterozygous individual carrying only a single dose of M. Antithetical antigens C/c, E/e, M/N, S/s, and Jk^a/Jk^b commonly show dosage. Dosage is less obvious with D, K/k, and Lu^a/Lu^b antigens. It typically is more apparent within a family than between families. Dosage within the Duffy system also may not be serologically obvious because Fy(a+b–) or Fy(a–b+) phenotypes are seen in either homozygous (Fy^aFy^a or Fy^bFy^b) or heterozygous (Fy^aFy or Fy^bFy) individuals.

        Some blood group antigens are inherited as closely linked genes or haplotypes. Haplotype pairings and gene interaction (either cis or trans) also can affect phenotypic expression. For example, the pairing of C in trans position to D can result in weak expression of D (see "Rh Blood Group System" above), whereas E in cis position with D is associated with strong expression of D. Among the common phenotypes, R₂R₂ RBCs carry the strongest expression of D. In the Kell system, Kp^a is associated with weakened expression of cis k and Js^b.

       Still other antigens are affected by regulator genes. In(Lu) is a dominant inhibitor gene that suppresses expression of Lutheran, P1, i, and many other antigens. The dominant inhibitor In(Jk) suppresses expression of Jk^a and Jk^b antigens. Rare variants of the RHAG gene depress or prevent expression of the Rh antigens (see "Rhnull Syndrome" below).