title: Molecular basis of the Rh antigen RH48 (JAL).
abstract: OBJECTIVE
  RH48 (JAL) is a low-incidence Rh antigen of unknown molecular background associated with weakened expression of RhCE antigens. The objective of this study was to establish the molecular basis of JAL.
  
  
  METHODS
  Seventeen JAL+ samples, from seven black (one of them a Brazilian of mixed race: black/Caucasian), nine European Caucasians and one Asian individuals, were typed with anti-D, -C, -c, -E and -e. Some samples were also tested for V/VS and ce (f). Titration studies and flow cytometry were used to analyse the expression of the JAL antigen and genomic DNA sequencing of all RHCE exons was conducted on all samples. Routine genotyping for RHCE was carried out on all samples. Screening of RHD exons 1-10, which included detection of the DAU allele, was carried out on all except one of the black samples. The Caucasian samples and remaining black sample were screened for the DAU mutation 1136C>T (T379M).
  
  
  RESULTS
  Six black individuals had the Dce haplotype with RHCE mutations 340C>T (R114W) and 733C>G (L245V) [V/VS] and the RHD mutation T379M [DAU]. One mixed race individual had the Dce haplotype with the RHCE mutation 340C>T (R114W) but without the V/VS or DAU mutation. Eight Caucasians had the DCe haplotype with the 340C>T mutation. One Caucasian and one Asian had the Dce haplotype with a different mutation in an adjacent nucleotide, 341G>A (R114Q). All Caucasian individuals were negative for the DAU mutation 1136C>T (T379M). Previously described weakness of CE-related Rh antigens when present in single dose on JAL+ samples of DCe and Dce haplotypes was observed. Weak expression of V/VS was observed in the three black samples tested and weakness of JAL was observed in the black samples compared to the Caucasian samples.
  
  
  CONCLUSIONS
  The same mutation (340C>T, R114W) in two different haplotypes (DCe and Dce) and another mutation (341G>A, R114Q) in one of these haplotypes (Dce) are associated with expression of the JAL antigen. One of the RHCE mutations detected in our samples (340C>T) has been previously described but not in association with the JAL antigen. Our results indicate that the previously described RhCeMA and ce(s)(340) alleles encode the JAL antigen. Expression of V/VS antigen is weakened in the presence of JAL and expression of JAL is usually weaker when associated with the Dce haplotype compared to DCe.
authors.affiliation: Blood Transfusion Service SRC Bern, Murtenstrasse 133, Berne, Switzerland. hein.hustinx@bsd-be.ch
authors.forename: H
authors.initials: H
authors.lastname: Hustinx
authors.forename: J
authors.initials: J
authors.lastname: Poole
authors.forename: P
authors.initials: P
authors.lastname: Bugert
authors.forename: P
authors.initials: P
authors.lastname: Gowland
authors.forename: F
authors.initials: F
authors.lastname: Still
authors.forename: S
authors.initials: S
authors.lastname: Fontana
authors.forename: E A
authors.initials: EA
authors.lastname: Scharberg
authors.forename: L
authors.initials: L
authors.lastname: Tilley
authors.forename: G
authors.initials: G
authors.lastname: Daniels
authors.forename: C
authors.initials: C
authors.lastname: Niederhauser
mesh_terms: D000483:Alleles; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D044469:Racial Groups; D012204:Rh-Hr Blood-Group System / Q000096:biosynthesis* / Q000235:genetics*
chemical_list: C066468:RHCE protein, human; D012204:Rh-Hr Blood-Group System