Defining the Jr (a–) phenotype in the J apanese population

• Published in: Transfusion (Philadelphia, Pa.) Vol. 54; no. 2; pp. 412 - 417
• Main Authors: Tanaka, Mitsunobu, Kamada, Ikuko, Takahashi, Junko, Kimura, Keiko, Matsukura, Harumichi, Tani, Yoshihiko
• Format: Journal Article
• Language: English
• Published: 01.02.2014
• ISSN: 0041-1132; 1537-2995
• DOI: 10.1111/trf.12277

Background The Jr(a–) phenotype is rare in E uropean and N orth A merican 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 G 2 ( ABCG 2 ) gene and concluded that ABCG 2 ‐null alleles encode the Jr(a–) phenotype. In J apanese R ed C ross B lood C enters, 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 J apan, in addition to serologic typing. Study Design and Methods Purified genomic DNA extracts of J apanese donor samples [500 Jr(a+) and 85 Jr(a–) phenotypes] were amplified using specific amplification primers for the c .376 C > T mutation, which is the most common mutation in the Asian JR null 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 .376 C > T ( Gln 126 Stop ) change. In other samples, two novel null alleles were detected: c .2 T > C and c .421 C > A : c .1515 delC . Conclusion I n this study, more than 90% of the J apanese Jr(a–) phenotypes had c .376 C > T ( Gln 126 Stop ) nucleotide change. In the other Jr(a–) , a new mutation ( c .2T> C ) in the start codon encoding Thr instead of Met , c .1515 delC encoding A la505 A lafs S top and heterozygous for c .337 C / T and c .736 C / T were detected. DNA ‐based genotyping is accurate and useful for Jr(a–) donor typing.