title: A novel St(a) glycophorin produced via gene conversion of pseudoexon III from glycophorin E to glycophorin A gene.
abstract: Stone (St(a)) is a variant antigen carried on human erythrocyte MNSs glycophorins (GPSt(a)) that are genetically associated with splicing mutations in GPA genes or with hybrid formation between GPA and GPB genes. Here we identify the first and rare gene conversion event in which GPE, the third member of the family, recombined with GPA, giving rise to a GPA-E-A hybrid gene encoding the St(a) antigen. Western blot detected expression in the proband of both GPA and GPSt(a) on the plasma membrane. Southern blot showed a new restriction fragment from the GPSt(a) gene, indicating an altered exon III-intron 3 junction. Sequencing of RT-PCR products identified one full-length and two shortened glycophorin cDNAs. The shortened forms were derived from GPSt(a) lacking one (exon III) and two exons (exon III and IV), respectively. To define the molecular basis for exon skipping, the genomic region spanning exon III of the GPSt(a) gene was amplified and sequenced. This revealed transfer from GPE to GPA of a DNA segment containing the pseudoexon III and its silent donor splice site. Thus, the inactivation of GPA exon III by conversion of a silent GPE donor splice site portrays a new molecular mechanism for St(a) antigen expression in human erythrocytes.
authors.affiliation: Laboratory of Biochemistry and Molecular Genetics, Lindsley F. Kimball Research Institute, New York Blood Center, New York, New York 10021, USA. chuang@nybc.org
authors.forename: C H
authors.initials: CH
authors.lastname: Huang
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.forename: O O
authors.initials: OO
authors.lastname: Blumenfeld
mesh_terms: D000483:Alleles; D017398:Alternative Splicing; D001483:Base Sequence; D015139:Blotting, Southern; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D005091:Exons; D006021:Glycophorins / Q000737:chemistry / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D020033:Protein Isoforms; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid
chemical_list: D018076:DNA, Complementary; D006021:Glycophorins; D020033:Protein Isoforms; D012333:RNA, Messenger; C064318:glycophorin Stone