title: A functional AQP1 allele producing a Co(a-b-) phenotype revises and extends the Colton blood group system.
abstract: BACKGROUND
  The Colton blood group system currently comprises three antigens, Co(a) , Co(b) , and Co3. The latter is only absent in the extremely rare individuals of the Colton "null" phenotype, usually referred to as Co(a-b-), which lack the water channel AQP1 that carries the Colton antigens. The discovery of a Co(a-b-) individual with no AQP1 deficiency suggested another molecular basis for the Co(a-b-) phenotype.
  
  
  METHODS
  Red blood cells were analyzed by stopped-flow light scattering and Western blotting and typed by hemagglutination and flow cytometry. Genotyping by sequencing and polymerase chain reaction-restriction fragment length polymorphism was applied. An expression system for Colton antigens was developed in mammalian cells.
  
  
  RESULTS
  Although Co(a-b-), the proband expressed fully functional AQP1 and had developed a novel Colton alloantibody. Sequencing of AQP1 revealed a homozygous nucleotide change (140A>G) encoding the single-amino-acid substitution Q47R. A second case was identified due to the presence of this novel Colton alloantibody. By generating an expression system for Colton antigens in K-562 cells, the Q47R substitution was shown to inhibit the expression of both Co(a) and Co(b) antigens. Other naturally occurring single-amino-acid substitutions, that is, A45T, P38L, and N192K, were also studied in this Colton antigen expression system.
  
  
  CONCLUSIONS
  The Co(a-b-) phenotype can be generated by a functional AQP1 allele, that is, AQP1 140G encoding AQP1 (Q47R) and allowing the development of a novel Colton alloantibody. This study also shows that the Co(b) antigen can be produced by at least two different substitutions at Amino Acid Position 45, that is, A45V and A45T.
authors.affiliation: National Institute of Blood Transfusion, INTS, Paris, France. larnaud@ints.fr
authors.forename: Lionel
authors.initials: L
authors.lastname: Arnaud
authors.forename: Virginie
authors.initials: V
authors.lastname: Helias
authors.forename: Cécile
authors.initials: C
authors.lastname: Menanteau
authors.forename: Thierry
authors.initials: T
authors.lastname: Peyrard
authors.forename: Nicole
authors.initials: N
authors.lastname: Lucien
authors.forename: Pierre
authors.initials: P
authors.lastname: Ripoche
authors.forename: Régine
authors.initials: R
authors.lastname: Lapègue
authors.forename: Bach-Nga
authors.initials: BN
authors.lastname: Pham
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Le Pennec
authors.forename: John J
authors.initials: JJ
authors.lastname: Moulds
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Cartron
mesh_terms: D000483:Alleles; D051398:Aquaporin 1 / Q000235:genetics* / Q000276:immunology*; D001789:Blood Group Antigens / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005838:Genotype; D006801:Humans; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010641:Phenotype; D016133:Polymerase Chain Reaction
chemical_list: C496020:AQP1 protein, human; D001789:Blood Group Antigens; D051398:Aquaporin 1