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
AU - Wang, Ya Hui
AU - Lin, Kuan Tsou
AU - Wu, Hua Lin
AU - Lin, Tsun Mei
PY - 2010/6
Y1 - 2010/6
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.
UR - http://www.scopus.com/inward/record.url?scp=77952312473&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77952312473&partnerID=8YFLogxK
U2 - 10.1016/j.bbagen.2010.02.006
DO - 10.1016/j.bbagen.2010.02.006
M3 - Article
C2 - 20188798
AN - SCOPUS:77952312473
SN - 0304-4165
VL - 1800
SP - 565
EP - 573
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 6
ER -