The JR blood group system: identification of alleles that alter expression

Background The ABCG 2 gene encodes antigens of the JR blood group system. Red blood cells ( RBCs ) from individuals homozygous for ABCG 2 null alleles are nonreactive with polyclonal and monoclonal anti‐ Jr a . However, some RBC s have been defined as Jr (a+ W /–) or Jr (a–), particularly when tested with polyclonal anti‐ Jr a . In an effort to resolve these apparent serologic ambiguities, the current study was undertaken. Study Design and Methods Hemagglutination of RBC s from two individuals known to express a single copy of functional ABCG 2 were compared to RBC s from eight unrelated, previously characterized, Jr(a+ W /–) donors. Standard polymerase chain reaction–based methods were used to characterize ABCG 2 alleles. Results Two monoclonal anti‐ Jr a clones agglutinated RBCs from the eight Jr(a+ W /–) study subjects. Two of these subjects were homozygous for a missense ABCG 2 change (c.1858 A ; A sp620 A sn). Two were heterozygous for two missense changes; one was c.1858 G > A and c.421 C > A ( A sp620Asn; G ln141 L ys), and the other was c.1714 A > C and c.421 C > A ( S er572 A rg; G ln141 L ys). The remaining four subjects were heterozygous for c.421 C > A (Gln141 L ys), and for one of four null alleles. Conclusions We have identified three ABCG 2 alleles that are newly associated with weakened Jr a expression. One of these is novel, the missense allele c.1714 A > C ( S er572 A rg) and two that have been previously described c.421 C > A (rs2231142; G ln141 L ys) and c.1858 G > A (rs34783571; A sp620 A sn). In addition, we found a novel, presumed null allele, c.1017_1019del CTC ( S er340del).