title: Gene conversion confined to a direct repeat of the acceptor splice site generates allelic diversity at human glycophorin (GYP) locus.
abstract: The glycophorin locus (GYP) on the long arm of chromosome 4 encodes antigens of the MNSs blood group system and displays considerable allelic variation among human populations. The genomic structure and organization of a variant glycophorin allele specifying a novel Miltenberger (Mi)-related phenotype, MiX, were examined. This variant probably arose from a gene conversion event involving a direct repeat of the acceptor splice site. Southern blot analysis indicated that MiX gene derived its 5' and 3' portions from glycophorin B or delta gene but its internal part from glycophorin A or alpha gene. Genomic sequences encompassing the rearranged regions of the MiX gene were amplified by single copy polymerase chain reaction. Direct DNA sequencing showed that during the formation of MiX gene, a short stretch of alpha exon III with a donor splice site has replaced a silent sequence in the delta gene containing a cryptic acceptor splice site. The upstream delta-alpha breakpoint is flanked by the direct repeats of the acceptor splice site, whereas the down-stream alpha-delta breakpoint is located in the adjacent intron. This segmental transfer produced a new composite exon whose expression not only transactivated a portion of silent sequence but also created intraexon and interexon hybrid junctions that characterize the antigenic specificities of MiX glycophorin. The identification of MiX as yet another delta-alpha-delta hybrid different from MiIII and MiVI in gene conversion sites suggests that shuffling of expressed and unexpressed sequences through particular genomic DNA motifs has been an important mechanism for shaping the antigenic diversity of MNSs blood group system during evolution.
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461.
authors.forename: C H
authors.initials: CH
authors.lastname: Huang
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.forename: J
authors.initials: J
authors.lastname: McCreary
authors.forename: O O
authors.initials: OO
authors.lastname: Blumenfeld
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D015139:Blotting, Southern; D002894:Chromosomes, Human, Pair 4; D004247:DNA / Q000097:blood / Q000235:genetics / Q000302:isolation & purification; D005784:Gene Amplification; D005785:Gene Conversion; D014644:Genetic Variation; D006021:Glycophorins / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008951:MNSs Blood-Group System / Q000235:genetics; D008969:Molecular Sequence Data; D012326:RNA Splicing; D012091:Repetitive Sequences, Nucleic Acid; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid
chemical_list: D006021:Glycophorins; D008951:MNSs Blood-Group System; D004247:DNA