title: Molecular basis for H blood group deficiency in Bombay (Oh) and para-Bombay individuals.
abstract: The penultimate step in the biosynthesis of the human ABO blood group oligosaccharide antigens is catalyzed by alpha-(1,2)-fucosyltransferase(s) (GDP-L-fucose: beta-D-galactoside 2-alpha-L-fucosyltransferase, EC 2.4.1.69), whose expression is determined by the H and Secretor (SE) blood group loci (also known as FUT1 and FUT2, respectively). These enzymes construct Fuc alpha 1-->2Gal beta-linkages, known as H determinants, which are essential precursors to the A and B antigens. Erythrocytes from individuals with the rare Bombay and para-Bombay blood group phenotypes are deficient in H determinants, and thus A and B determinants, as a consequence of apparent homozygosity for null alleles at the H locus. We report a molecular analysis of a human alpha-(1,2)-fucosyltransferase gene, thought to correspond to the H blood group locus, in a Bombay pedigree and a para-Bombay pedigree. We find inactivating point mutations in the coding regions of both alleles of this gene in each H-deficient individual. These results define the molecular basis for H blood group antigen deficiency in Bombay and para-Bombay phenotypes, provide compelling evidence that this gene represents the human H blood group locus, and strongly support a hypothesis that the H and SE loci represent distinct alpha-(1,2)-fucosyltransferase genes. Candidate sequences for the human SE locus are identified by low-stringency Southern blot hybridization analyses, using a probe derived from the H alpha-(1,2)-fucosyltransferase gene.
authors.affiliation: Howard Hughes Medical Institute, University of Michigan, Ann Arbor 48109-0650.
authors.forename: R J
authors.initials: RJ
authors.lastname: Kelly
authors.forename: L K
authors.initials: LK
authors.lastname: Ernst
authors.forename: R D
authors.initials: RD
authors.lastname: Larsen
authors.forename: J G
authors.initials: JG
authors.lastname: Bryant
authors.forename: J S
authors.initials: JS
authors.lastname: Robinson
authors.forename: J B
authors.initials: JB
authors.lastname: Lowe
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics*; D000483:Alleles; D001483:Base Sequence; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D005091:Exons; D005260:Female; D005647:Fucosyltransferases / Q000172:deficiency* / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007438:Introns; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D015183:Restriction Mapping; D000097631:Galactoside 2-alpha-L-fucosyltransferase
chemical_list: D000017:ABO Blood-Group System; D017931:DNA Primers; D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase