Inversion region for hypertension and brachydactyly on chromosome 12p features multiple splicing and noncoding RNA

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Item Type:	Article
Title:	Inversion region for hypertension and brachydactyly on chromosome 12p features multiple splicing and noncoding RNA
Creators Name:	Bähring, S., Kann, M., Neuenfeld, Y., Gong, M., Chitayat, D., Toka, H.R., Toka, O., Plessis, G., Maass, P., Rauch, A., Aydin, A. and Luft, F.C.
Abstract:	Autosomal-dominant hypertension and brachydactyly (Online Mendelian Inheritance in Man 112410) is a prototype-translational research project. We used interphase fluorescent in situ hybridization and discovered complex rearrangements on chromosome 12p in 5 families but elucidated a common inverted region in the linkage interval. The inversion contains no known gene. However, we found 5 expressed sequence tags in databases. We used 5'- and 3'-Rapid Amplification of cDNA Ends PCR for elongation of the transcripts in phenotype-relevant tissue (fetal aorta, fetal brain, and fetal cartilage). We detected tissue-specific multiple splicing with different exon usage of 32 exons in the gene-related structure. These different transcripts lack both open reading frames and Kozak sequences. In vitro transcription/translation experiments did not identify any peptide-related molecules. We then performed quantitative RT-PCR to test for differential expression of the various spliced transcripts in the total fibroblast RNA of affected and nonaffected Turkish family members. Skin fibroblasts of affected individuals have a significantly increased proliferation rate compared with nonaffected individuals. Ten of 12 spliced exon combinations representing all of the spliced variants do not show a significantly different RNA expression rate. However, 2 RT-PCR products are exclusively expressed in nonaffected individuals. Both reverse transcription amplicons share 1 exon. This result is surprising because of the autosomal-dominant mode of inheritance of the trait. RNA secondary prediction of this single exon results in a stable stem-loop structure known to be essential for microRNA processing. We are pursuing the possibility of microRNA expression in affected patients that leads to complete down regulation of a spliced transcript.
Keywords:	Hypertension, Genetics, Mendelian, Chromosomal rearrangements, Translational research
Source:	Hypertension
ISSN:	0194-911X
Publisher:	American Heart Association
Volume:	51
Number:	2
Page Range:	426-431
Date:	February 2008
Official Publication:	https://doi.org/10.1161/HYPERTENSIONAHA.107.101774
PubMed:	View item in PubMed

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