Aberrant RNA splicing in RHD 7-9 exons of DEL individuals in Taiwan: A mechanism study

Hsiang Chun Liu, Hock Liew Eng, Yu Fen Yang, Ya Hui Wang, Kuan Tsou Lin, Hua-Lin Wu, Tsun Mei Lin

Research output: Contribution to journalArticle

11 Citations (Scopus)

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 inved 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.

Original languageEnglish
Pages (from-to)565-573
Number of pages9
JournalBiochimica et Biophysica Acta - General Subjects
Volume1800
Issue number6
DOIs
Publication statusPublished - 2010 Jun 1

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RNA Splicing
Taiwan
Exons
RNA
Alleles
Phenotype
Polymorphism
Immunization
Messenger RNA
Introns
Haplotypes
Single Nucleotide Polymorphism
Nucleotides
Genes
Odds Ratio
Mutation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology

Cite this

Liu, Hsiang Chun ; Eng, Hock Liew ; Yang, Yu Fen ; Wang, Ya Hui ; Lin, Kuan Tsou ; Wu, Hua-Lin ; Lin, Tsun Mei. / Aberrant RNA splicing in RHD 7-9 exons of DEL individuals in Taiwan : A mechanism study. In: Biochimica et Biophysica Acta - General Subjects. 2010 ; Vol. 1800, No. 6. pp. 565-573.
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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 inved 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.",
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Aberrant RNA splicing in RHD 7-9 exons of DEL individuals in Taiwan : A mechanism study. / Liu, Hsiang Chun; Eng, Hock Liew; Yang, Yu Fen; Wang, Ya Hui; Lin, Kuan Tsou; Wu, Hua-Lin; Lin, Tsun Mei.

In: Biochimica et Biophysica Acta - General Subjects, Vol. 1800, No. 6, 01.06.2010, p. 565-573.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Aberrant RNA splicing in RHD 7-9 exons of DEL individuals in Taiwan

T2 - A mechanism study

AU - Liu, Hsiang Chun

AU - Eng, Hock Liew

AU - Yang, Yu Fen

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AU - Lin, Kuan Tsou

AU - Wu, Hua-Lin

AU - Lin, Tsun Mei

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N2 - 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 inved 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.

AB - 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 inved 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.

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