title: Molecular genetic analysis of ABO blood group variations reveals 29 novel ABO subgroup alleles.
abstract: BACKGROUND
  Identifying genetic variants of the ABO gene may reveal new biologic mechanisms underlying variant phenotypes of the ABO blood group. We report the molecular genetic analysis of 322 apparently unrelated ABO subgroup individuals in an estimated 2.1 million donors.
  
  
  METHODS
  We performed phenotype investigations by serology studies, analyzed the DNA sequence of the ABO gene by direct sequencing or sequencing after cloning, and evaluated promoter activity by reporter assays.
  
  
  RESULTS
  In 62 rare ABO alleles, we identified 29 novel ABO subgroup alleles in 43 apparently unrelated subgroup individuals and their four available pedigrees. Of these alleles, one was a deletion-mutation allele, four were hybrid alleles, and 24 were point-mutation alleles. Most of the point mutations were detected in Exons 6 to 7, while several others were also detected in Exons 1 to 5 or splicing regions. One ABO promoter mutation, -35 to -18 del, was found and verified to reduce promoter activity, as determined by dual luciferase assays. Two mutations, 7G>T and 52C>T, carrying the premature terminal codons E3X and R18X in the 5'-region, were found to be associated with the very weak ABO subgroups "Ael" and "Bel."
  
  
  CONCLUSIONS
  Twenty-nine ABO subgroup alleles were newly linked to different kinds of ABO variations. We provide the first evidence that promoter abnormality is involved in the formation of weak ABO phenotypes. We also described the first naturally occurring ABO alleles with premature terminal codons in the 5'-region that led to Ael and Bel phenotypes.
authors.affiliation: Blood Group Reference Laboratory, Shanghai Institute of Blood Transfusion, Shanghai Blood Center; Blood Transfusion Department, Ruijin Hospital, Medical School of Shanghai Jiao Tong University, Shanghai, China; Blood Group Laboratory, Tanggu Blood Center, Tianjin, China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Cai
authors.forename: Sha
authors.initials: S
authors.lastname: Jin
authors.forename: Xi
authors.initials: X
authors.lastname: Liu
authors.forename: Liangfeng
authors.initials: L
authors.lastname: Fan
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lu
authors.forename: Jianlian
authors.initials: J
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Shen
authors.forename: Songsong
authors.initials: S
authors.lastname: Gong
authors.forename: Li
authors.initials: L
authors.lastname: Qiu
authors.forename: Dong
authors.initials: D
authors.lastname: Xiang
mesh_terms: D000017:ABO Blood-Group System / Q000145:classification / Q000235:genetics* / Q000276:immunology; D000483:Alleles; D001782:Blood Donors; D005787:Gene Frequency; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D020014:K562 Cells; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000502:physiology; D017422:Sequence Analysis, DNA; D012698:Serologic Tests; D014162:Transfection
chemical_list: D000017:ABO Blood-Group System