title: Long non-coding RNA expression profiles in hereditary haemorrhagic telangiectasia.
abstract: Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominantly inherited vascular disease characterized by the presence of mucocutaneous telangiectasia and arteriovenous malformations in visceral organs. HHT is predominantly caused by mutations in ENG and ACVRL1, which both belong to the TGF-β signalling pathway. The exact mechanism of how haploinsufficiency of ENG and ACVRL1 leads to HHT manifestations remains to be identified. As long non-coding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression and constitute a sizable fraction of the human transcriptome, we wanted to assess whether lncRNAs play a role in the molecular pathogenesis of HHT manifestations. By microarray technology, we profiled lncRNA transcripts from HHT nasal telangiectasial and non-telangiectasial tissue using a paired design. The microarray probes were annotated using the GENCODE v.16 dataset, identifying 4,810 probes mapping to 2,811 lncRNAs. Comparing HHT telangiectasial tissue with HHT non-telangiectasial tissue, we identified 42 lncRNAs that are differentially expressed (q<0.001). Using GREAT, a tool that assumes cis-regulation, we showed that differently expressed lncRNAs are enriched for genomic loci involved in key pathways concerning HHT. Our study identified lncRNAs that are aberrantly expressed in HHT telangiectasia and indicates that lncRNAs may contribute to regulate protein-coding loci in HHT. These results suggest that the lncRNA component of the transcriptome deserves more attention in HHT. A deeper understanding of lncRNAs and their role in telangiectasia formation possesses potential for discovering therapeutic targets in HHT.
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Otorhinolaryngology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Pernille M
authors.initials: PM
authors.lastname: Tørring
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Human Genetics, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Martin Jakob
authors.initials: MJ
authors.lastname: Larsen
authors.affiliation: Department of Otorhinolaryngology, Odense University Hospital, Odense, Denmark; Otorhinolaryngology, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Anette D
authors.initials: AD
authors.lastname: Kjeldsen
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Human Genetics, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Lilian Bomme
authors.initials: LB
authors.lastname: Ousager
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Epidemiology, Biostatistics and Bio-demography, Institute of Public Health, University of Southern Denmark, Odense, Denmark.
authors.forename: Qihua
authors.initials: Q
authors.lastname: Tan
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; Human Genetics, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
authors.forename: Klaus
authors.initials: K
authors.lastname: Brusgaard
mesh_terms: D030301:Activin Receptors, Type II / Q000235:genetics; D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D016000:Cluster Analysis; D000071063:Endoglin; D005260:Female; D020869:Gene Expression Profiling; D063990:Gene Ontology; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010641:Phenotype; D062085:RNA, Long Noncoding / Q000145:classification / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics; D013683:Telangiectasia, Hereditary Hemorrhagic / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D015703:Antigens, CD; C064206:ENG protein, human; D000071063:Endoglin; D062085:RNA, Long Noncoding; D011956:Receptors, Cell Surface; C425364:ACVRL1 protein, human; D030301:Activin Receptors, Type II