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

Background The ABCG2 gene encodes antigens of the JR blood group system. Red blood cells (RBCs) from individuals homozygous for ABCG2 null alleles are nonreactive with polyclonal and monoclonal anti-Jra. However, some RBCs have been defined as Jr(a+W/–) or Jr(a–), particularly when tested with polyclonal anti-Jra. In an effort to resolve these apparent serologic ambiguities, the current study was undertaken. Study Design and Methods Hemagglutination of RBCs from two individuals known to express a single copy of functional ABCG2 were compared to RBCs from eight unrelated, previously characterized, Jr(a+W/–) donors. Standard polymerase chain reaction–based methods were used to characterize ABCG2 alleles. Results Two monoclonal anti-Jra clones agglutinated RBCs from the eight Jr(a+W/–) study subjects. Two of these subjects were homozygous for a missense ABCG2 change (c.1858A; Asp620Asn). Two were heterozygous for two missense changes; one was c.1858G>A and c.421C>A (Asp620Asn; Gln141Lys), and the other was c.1714A>C and c.421C>A (Ser572Arg; Gln141Lys). The remaining four subjects were heterozygous for c.421C>A (Gln141Lys), and for one of four null alleles. Conclusions We have identified three ABCG2 alleles that are newly associated with weakened Jra expression. One of these is novel, the missense allele c.1714A>C (Ser572Arg) and two that have been previously described c.421C>A (rs2231142; Gln141Lys) and c.1858G>A (rs34783571; Asp620Asn). In addition, we found a novel, presumed null allele, c.1017_1019delCTC (Ser340del).