A novel Sta glycophorin produced via gene conversion of pseudoexon III from glycophorin E to glycophorin A gene

• Published in: Human mutation Vol. 15; no. 6; pp. 533 - 540
• Main Authors: Huang, Cheng-Han, Chen, Ying, Blumenfeld, Olga O.
• Format: Journal Article
• Language: English
• Published: New York John Wiley & Sons, Inc 01-06-2000; Hindawi Limited
• Subjects: gene conversion; glycophorins; GYPA; MNSs blood groups; red cells
• ISSN: 1059-7794; 1098-1004
• DOI: 10.1002/1098-1004(200006)15:6<533::AID-HUMU5>3.0.CO;2-R

Stone (Sta) is a variant antigen carried on human erythrocyte MNSs glycophorins (GPSta) 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 Sta antigen. Western blot detected expression in the proband of both GPA and GPSta on the plasma membrane. Southern blot showed a new restriction fragment from the GPSta 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 GPSta 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 GPSta 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 Sta antigen expression in human erythrocytes. Hum Mutat 15:533–540, 2000. © 2000 Wiley‐Liss, Inc.