A novel JKA allele, nt561C>A, associated with silencing of Kidd expression

BACKGROUND: The Jk(a−b−) null phenotype is not common but is more prevalent in Polynesian and Asian persons and appears to be rare in blacks. We determined the molecular basis for Jk(a−b−) in an African American family. DNA testing of samples from random African American, Caucasian, and Brazilian blacks was done to estimate the allele frequency. STUDY DESIGN AND METHODS: Standard methods were used for red blood cell (RBC) typing. DNA was isolated from white blood cells, and polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) and amplification and sequencing of the coding regions of JK were performed by routine molecular methods. A MaeIII PCR‐RFLP assay was designed to target the nucleotide (nt) change. RESULTS: RBCs from the proband typed as Jk(a−b−) and DNA testing indicated JK*A/JK*A. JK sequencing found that the sample was homozygous for nt561C>A change, predicted to encode a premature stop in the protein (187Stop). The altered allele was present in the heterozygous state in three of six siblings. Testing of 500 African American and 100 Caucasian donors from the same region and 500 African American donors from the southern United States found no additional examples. Screening of 1174 Brazilian blacks revealed seven examples: one homozygote and six heterozygotes. CONCLUSIONS: JK*A (561C>A) is associated with a Kidd‐null phenotype in this African American family. The allele was present in approximately one in 168 Brazilian blacks, suggesting that detection of this allele is important to avoid false‐positive prediction of Jk(a) status in this population.