Molecular basis of the K:6,‐7 [Js(a+b−)] phenotype in the Kell blood group system

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Abstract
BACKGROUND: The Kell blood group system consists of at least 21 antigens. KEL6(Jsa) is a low‐incidence antigen that has an antithetical relationship with the high‐incidence KEL7(Jsb) antigen. The molecular basis of KEL6 that appears in less than 1.0 percent of the general population, but in up to 19.5 percent of African Americans, was unknown. STUDY DESIGN AND METHODS: Nineteen exons of the Kell gene (KEL) were amplified by polymerase chain reaction (PCR) assays of genomic DNA obtained from individuals with K:6,‐7 [Js(a+b‐)] phenotype. The PCR products were sequenced. A comparison was made of the sequence of the PCR products and the sequence of K:‐6,7, the common phenotype. RESULTS: KEL from individuals with the K:6,‐7 phenotype had two base substitutions in exon 17. One was a missense mutation (T‐to‐C base substitution) at nucleotide (nt) 1910, which predicts an amino acid change from leucine to proline; the other was a silent substitution (A‐ to‐C) at nt 2019. The T‐to‐C substitution eliminated a restriction site for Mnl I, whereas the A‐to‐G substitution eliminated a Dde I site. Analyses of exon 17 in seven unrelated persons with K:6,‐7 phenotype by Mnl I and Dde I enzymes showed the expected presence of restriction fragment length polymorphisms. CONCLUSION: The base substitutions T‐to‐ C at nt 1910 and A‐to‐G at nt 2019 are unique to KEL6. The predicted Leu–>Pro change may disrupt the alpha‐helical structure and thus form the epitope for KEL6.
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