title: Aberrant RNA splicing in RHD 7-9 exons of DEL individuals in Taiwan: a mechanism study.
abstract: BACKGROUND
  The Rh blood D group provides a clinically important model of aberrant splicing with skipped exons. Approximately 30% of serologically D-negative Chinese individuals have an intact RHD gene (DEL phenotype) and induce allo-immunization in transfusions. The RHD1227GNA polymorphism occurs in >95% DEL phenotype of Asian descent. The effects of RHD 1227A and a novel allele on exon 9 splicing were examined.
  
  
  RESULTS
  Amplified DEL RNA products revealed that 3 transcripts involved skipping of exons 8-9, exon 9, or exon 9 with an inserted 170-bp cryptic exon located between exons 7 and 8. A novel, single nucleotide polymorphism was identified in the 7th intron, (IVS7) 923C>T, and present in all DEL patients. The odds ratio of RHD1227G>A allele with DEL phenotype was 2711. Splicing analysis of transcripts from minigenes containing the 1227GNA allele, but not the (IVS7) 923C>T allele, demonstrated aberrant exon 9 skipping.
  
  
  CONCLUSIONS
  A combined haplotype of 1227G>A and IVS7 923C>T alleles was apparent in >95% DEL Chinese individuals. RHD1227A mutation significantly increased aberrant mRNA splicing, producing a hybrid RHD mRNA lacking exon 9. These results provide a molecular basis of the DEL phenotype in the Chinese population.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Hsiang-Chun
authors.initials: HC
authors.lastname: Liu
authors.forename: Hock-Liew
authors.initials: HL
authors.lastname: Eng
authors.forename: Yu-Fen
authors.initials: YF
authors.lastname: Yang
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Wang
authors.forename: Kuan-Tsou
authors.initials: KT
authors.lastname: Lin
authors.forename: Hua-Lin
authors.initials: HL
authors.lastname: Wu
authors.forename: Tsun-Mei
authors.initials: TM
authors.lastname: Lin
mesh_terms: D000483:Alleles; D001483:Base Sequence; D017931:DNA Primers; D005091:Exons; D006801:Humans; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D012204:Rh-Hr Blood-Group System / Q000235:genetics*; D013624:Taiwan
chemical_list: D017931:DNA Primers; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen