title: Point mutations characterize KEL10, the KEL3, KEL4, and KEL21 alleles, and the KEL17 and KEL11 alleles.
abstract: BACKGROUND
  The Kell blood group system is complex, consisting of five sets of alleles and expressing high- and low-incidence antigens and at least 11 other independently expressed antigens. The molecular basis of two sets of alleles: KEL1 (K) and KEL2 (k) and KEL6 (Jsa) and KEL7 (Jsb) have been elucidated as single-base mutations leading to amino acid changes. The molecular basis for the KEL3 (Kpa), KEL4 (Kpb), and KEL21 (Kpc) alleles, the KEL11(Cote) and KEL17(Wka) alleles, and for KEL10 (UIa) is now reported.
  
  
  METHODS
  Genomic DNA from unrelated individuals with KEL:3,-4,-21 [Kp(a+b-c-)], KEL:-3,-4,21 [Kp(a-b-c+)], KEL:17,-11, and KEL:10 (UIa) phenotypes was amplified by polymerase chain reaction (PCR) with primers for the 19 exons of KEL. The PCR products were sequenced and compared to the DNA sequences of a common Kell system phenotype, KEL:-3,4,-21,-17,-10. Base mutations found were confirmed by restriction fragment length polymorphism analysis in which DNA of unrelated persons with similar red cell phenotypes was used.
  
  
  RESULTS
  In all cases, single-base mutations were responsible for the expression of the various antigens. In KEL3 (Kpa), KEL4 (Kpb), and KEL21 (Kpc), point mutations at the same codon in exon 8, encoding amino acid residue 281, distinguish the three genes. KEL4 has the CGG codon for arginine, KEL3 has the TGG codon for tryptophan, and KEL21 has the CAG codon for glutamine. KEL17 has a T1025C mutation in exon 8, encoding a valine-to-alanine amino acid change at residue 302. KEL10 has an A1601T mutation in exon 13, encoding a glutamic acid-to-valine change at residue 494. In all cases, the point mutations created restriction enzyme sites, and PCR-based restriction fragment length polymorphisms confirmed that these point mutations occurred in unrelated persons with the same red cell phenotype.
  
  
  CONCLUSIONS
  Single-base substitutions characterize the KEL3, KEL21, KEL17, and KEL10 genes. The allelic relationship of KEL3, KEL4, and KEL21 was confirmed because the mutations occur in the same codon, expressing different amino acids. PCR-based restriction fragment length polymorphisms can be used to distinguish genotypes.
authors.affiliation: Lindsley F. Kimball Research Institute, New York Blood Center, New York, USA.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: X
authors.initials: X
authors.lastname: Wu
authors.forename: S
authors.initials: S
authors.lastname: Son
authors.forename: D
authors.initials: D
authors.lastname: Naime
authors.forename: M
authors.initials: M
authors.lastname: Reid
authors.forename: Y
authors.initials: Y
authors.lastname: Okubo
authors.forename: P
authors.initials: P
authors.lastname: Sistonen
authors.forename: C
authors.initials: C
authors.lastname: Redman
mesh_terms: D000409:Alanine / Q000235:genetics; D000483:Alleles; D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D003062:Codon; D004247:DNA / Q000097:blood* / Q000737:chemistry; D005091:Exons; D018698:Glutamic Acid / Q000235:genetics; D005973:Glutamine / Q000235:genetics; D006801:Humans; D007626:Kell Blood-Group System / Q000235:genetics*; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D017422:Sequence Analysis, DNA; D014364:Tryptophan / Q000235:genetics; D014633:Valine / Q000235:genetics
chemical_list: D003062:Codon; D007626:Kell Blood-Group System; D005973:Glutamine; D018698:Glutamic Acid; D014364:Tryptophan; D004247:DNA; D001120:Arginine; D014633:Valine; D000409:Alanine