Mutation analysis of TRPS1 gene including core promoter, 5'UTR, and 3'UTR regulatory sequences with insight into their organization
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články
PubMed
27826100
DOI
10.1016/j.cca.2016.11.007
PII: S0009-8981(16)30453-3
Knihovny.cz E-zdroje
- Klíčová slova
- Alternative splicing, Chromosomal rearrangement, Mutation, NGS, Promoter,
- MeSH
- 3' nepřekládaná oblast genetika MeSH
- 5' nepřekládaná oblast genetika MeSH
- dítě MeSH
- DNA vazebné proteiny chemie genetika MeSH
- dospělí MeSH
- haploinsuficience MeSH
- Langerův-Giedionův syndrom genetika MeSH
- lidé MeSH
- mladý dospělý MeSH
- mutační analýza DNA * MeSH
- předškolní dítě MeSH
- promotorové oblasti (genetika) genetika MeSH
- represorové proteiny MeSH
- sekvence aminokyselin MeSH
- sekvence nukleotidů MeSH
- transkripční faktory chemie genetika MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- 3' nepřekládaná oblast MeSH
- 5' nepřekládaná oblast MeSH
- DNA vazebné proteiny MeSH
- represorové proteiny MeSH
- transkripční faktory MeSH
- TRPS1 protein, human MeSH Prohlížeč
The TRPS1 protein is a potent regulator of proliferation, differentiation, and apoptosis. The TRPS1 gene aberrations are strongly associated with rare trichorhinophalangeal syndrome (TRPS) development. We have conducted MLPA analysis to capture deletion within the crucial 8q24.1 chromosomal region in combination with mutation analysis of TRPS1 gene including core promoter, 5'UTR, and 3'UTR sequences in nine TRPS patients. Low complexity or extent of untranslated regulatory sequences avoided them from analysis in previous studies. Amplicon based next generation sequencing used in our study bridge over these technical limitations. Finally, we have made extended in silico analysis of TRPS1 gene regulatory sequences organization. Single contiguous deletion and an intragenic deletion intervening several exons were detected. Mutation analysis revealed five TRPS1 gene aberrations (two structural rearrangements, two nonsense mutations, and one missense substitution) reaching the overall detection rate of 78%. Several polymorphic variants were detected within the analysed regulatory sequences but without proposed pathogenic effect. In silico analysis suggested alternative promoter usage and diverse expression effectivity for different TRPS1 transcripts. Haploinsufficiency of TRPS1 gene was responsible for most of the TRPS phenotype. Structure of TRPS1 gene regulatory sequences is indicative of generally low single allele expression and its tight control.
Department of Medical Genetics University Hospital Brno Cernopolni 212 9 625 00 Brno Czech Republic
Genetika Ostrava s r o Korenskeho 1317 12 702 00 Ostrava Czech Republic
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