title: The JAL antigen (RH48) is the result of a change in RHCE that encodes Arg114Trp.
abstract: BACKGROUND
  The JAL antigen (Rh48) was discovered more than 30 years ago when it caused hemolytic disease of the fetus and newborn in an African American family. A decade later it was found to cause hemolytic disease of the fetus and newborn in a Caucasian family. The presence of the same low-prevalence antigen in two different ethnic groups is rare, but additional JAL+ in both groups was subsequently identified. This study was undertaken to investigate the RH gene(s) responsible for expression of JAL and to determine the structural relationship between JAL and other Rh antigens.
  
  
  METHODS
  Samples from 17 JAL+ people were included: 2 Caucasian, 6 African American, 7 African Brazilian, 1 Caribbean, and 1 Puerto Rican. RHCE and RHD were investigated at the genomic level, and Rh cDNAs were cloned and sequenced for some samples.
  
  
  RESULTS
  Caucasian JAL+ probands had RHCE*Ce, while JAL+ probands with African ancestry had RHCE*ce, but all had a nucleotide 340C>T change in Exon 3 of RHCE predicted to encode Arg114Trp. The JAL-encoding RHCE*ce also had 733C>G (Leu245Val) and was linked to conventional RHD or to RHD*DAU0.
  
  
  CONCLUSIONS
  JAL+ results from a nucleotide 340C>T (Arg114Trp) on either a Ce or ce background. Homology modeling of the JAL+ RhCE protein suggests that the Arg-->Trp change eliminates a critical loop-stabilizing H-bond between the side chain of Arg114 and the e-specific amino acid Ala226. Additionally, accommodation of the bulky tryptophan would disrupt the conformation of the extracellular loops containing C/c- and e-specific amino acids, providing a structural hypothesis for the simultaneous altered expression of C/c, e, and V/VS antigens.
authors.affiliation: Molecular Blood Group and Platelet Testing Laboratory, American Red Cross, Penn-Jersey Region, Philadelphia, PA 19130, USA. westhoffc@usa.redcross.org
authors.forename: Connie M
authors.initials: CM
authors.lastname: Westhoff
authors.forename: Sunitha
authors.initials: S
authors.lastname: Vege
authors.forename: Dwane
authors.initials: D
authors.lastname: Wylie
authors.forename: Pam
authors.initials: P
authors.lastname: Nickle
authors.forename: Christine
authors.initials: C
authors.lastname: Lomas-Francis
authors.forename: Kim
authors.initials: K
authors.lastname: Hue-Roye
authors.forename: Marion E
authors.initials: ME
authors.lastname: Reid
mesh_terms: D019943:Amino Acid Substitution / Q000276:immunology; D000906:Antibodies / Q000097:blood / Q000235:genetics; D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D004252:DNA Mutational Analysis; D004912:Erythrocytes / Q000378:metabolism; D005838:Genotype; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D012204:Rh-Hr Blood-Group System / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014364:Tryptophan / Q000235:genetics
chemical_list: D000906:Antibodies; C066468:RHCE protein, human; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen; D014364:Tryptophan; D001120:Arginine