title: Molecular basis for the p phenotype. Identification of distinct and multiple mutations in the alpha 1,4-galactosyltransferase gene in Swedish and Japanese individuals.
abstract: p phenotype individuals lack both P(k) (Gb3) and P (Gb4) glycolipid antigens of the P blood group system. To explore the molecular basis for this phenotype, DNA sequences of Gb3 synthase (alpha1, 4-galactosyltransferase; alpha1,4Gal-T) in six p phenotype individuals from Japan and Sweden were analyzed. A missense mutation P251L and a nonsense mutation W261stop in three and one Japanese indivuiduals, respectively, and missense mutations M183K and G187D in one each of two Swedish p individuals were found, indicating that p individuals from Japan and Sweden have distinct and multiple homozygous point mutations in the coding region. In the function analysis of the mutated alpha1,4Gal-Ts by the transfection of the expression vectors, P251L and M183K mutations showed complete loss of enzyme function, and W261stop and G187D mutations resulted in the marginal activity. BLAST analysis of homologous sequences of alpha1, 4Gal-T revealed that three residues, Met(183), Gly(187), and Pro(251), at which missense mutations were found, were highly conserved among all species examined, suggesting their importance for the function of alpha1,4Gal-T.
authors.affiliation: Department of Biochemistry II, Nagoya University School of Medicine, Tsurumai, Nagoya 466-0065, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Furukawa
authors.forename: K
authors.initials: K
authors.lastname: Iwamura
authors.forename: M
authors.initials: M
authors.lastname: Uchikawa
authors.forename: B N
authors.initials: BN
authors.lastname: Sojka
authors.forename: J
authors.initials: J
authors.lastname: Wiels
authors.forename: T
authors.initials: T
authors.lastname: Okajima
authors.forename: T
authors.initials: T
authors.lastname: Urano
authors.forename: K
authors.initials: K
authors.lastname: Furukawa
mesh_terms: D000595:Amino Acid Sequence; D001483:Base Sequence; D017931:DNA Primers; D005700:Galactosyltransferases / Q000737:chemistry / Q000235:genetics*; D005828:Genetics, Population; D006801:Humans; D007564:Japan; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D010127:P Blood-Group System / Q000235:genetics*; D010641:Phenotype; D017386:Sequence Homology, Amino Acid; D013548:Sweden
chemical_list: D017931:DNA Primers; D010127:P Blood-Group System; D005700:Galactosyltransferases