Defining the Jr(a–) phenotype in the Japanese population

Background The Jr(a–) phenotype is rare in European and North American populations but is not so rare in Japanese and other Asian populations. Recently, two groups have established the connection between the Jr(a–) phenotype and the ATP-binding cassette, member G2 (ABCG2) gene and concluded that ABCG2-null alleles encode the Jr(a–) phenotype. In Japanese Red Cross Blood Centers, the Jr(a–) phenotype is found with a prevalence of 0.05% among blood donors, and we applied DNA-based genotyping to investigate the molecular basis of the Jr(a–) phenotype in Japan, in addition to serologic typing. Study Design and Methods Purified genomic DNA extracts of Japanese donor samples [500 Jr(a+) and 85 Jr(a–) phenotypes] were amplified using specific amplification primers for the c.376C>T mutation, which is the most common mutation in the Asian JRnull allele. Polymerase chain reaction products were examined by high-resolution melt techniques and DNA sequence analyses. Results Seventy-nine of 85 Jr(a–) samples were homozygous for the single-nucleotide polymorphism c.376C>T (Gln126Stop) change. In other samples, two novel null alleles were detected: c.2T>C and c.421C>A: c.1515delC. Conclusion In this study, more than 90% of the Japanese Jr(a–) phenotypes had c.376C>T (Gln126Stop) nucleotide change. In the other Jr(a–), a new mutation (c.2T>C) in the start codon encoding Thr instead of Met, c.1515delC encoding Ala505AlafsStop and heterozygous for c.337C/T and c.736C/T were detected. DNA-based genotyping is accurate and useful for Jr(a–) donor typing.