Aberrant RNA splicing in RHD 7-9 exons of DEL individuals in Taiwan: a mechanism study.
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.
Liu
Hsiang-Chun
HC
Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan.
Eng
Hock-Liew
HL
Yang
Yu-Fen
YF
Wang
Ya-Hui
YH
Lin
Kuan-Tsou
KT
Wu
Hua-Lin
HL
Lin
Tsun-Mei
TM
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
D017931:DNA Primers; D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen