-
Je něco špatně v tomto záznamu ?
Mutation analysis of TRPS1 gene including core promoter, 5'UTR, and 3'UTR regulatory sequences with insight into their organization
R. Solc, M. Klugerova, J. Vcelak, A. Baxova, M. Kuklik, J. Vseticka, R. Beharka, K. Hirschfeldova,
Jazyk angličtina Země Nizozemsko
Typ dokumentu časopisecké články
- 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
- 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
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
Citace poskytuje Crossref.org
- 000
- 00000naa a2200000 a 4500
- 001
- bmc17013414
- 003
- CZ-PrNML
- 005
- 20170427115758.0
- 007
- ta
- 008
- 170413s2017 ne f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1016/j.cca.2016.11.007 $2 doi
- 035 __
- $a (PubMed)27826100
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a ne
- 100 1_
- $a Solc, Roman $u Department of Anthropology and Human Genetics, Faculty of Science, Charles University in Prague, Vinicna 7, 128 43 Prague, Czech Republic. Electronic address: roman.solc@natur.cuni.cz.
- 245 10
- $a Mutation analysis of TRPS1 gene including core promoter, 5'UTR, and 3'UTR regulatory sequences with insight into their organization / $c R. Solc, M. Klugerova, J. Vcelak, A. Baxova, M. Kuklik, J. Vseticka, R. Beharka, K. Hirschfeldova,
- 520 9_
- $a 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.
- 650 _2
- $a 3' nepřekládaná oblast $x genetika $7 D020413
- 650 _2
- $a 5' nepřekládaná oblast $x genetika $7 D020121
- 650 _2
- $a dospělí $7 D000328
- 650 _2
- $a sekvence aminokyselin $7 D000595
- 650 _2
- $a sekvence nukleotidů $7 D001483
- 650 _2
- $a dítě $7 D002648
- 650 _2
- $a předškolní dítě $7 D002675
- 650 12
- $a mutační analýza DNA $7 D004252
- 650 _2
- $a DNA vazebné proteiny $x chemie $x genetika $7 D004268
- 650 _2
- $a ženské pohlaví $7 D005260
- 650 _2
- $a haploinsuficience $7 D057895
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a Langerův-Giedionův syndrom $x genetika $7 D015826
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a promotorové oblasti (genetika) $x genetika $7 D011401
- 650 _2
- $a transkripční faktory $x chemie $x genetika $7 D014157
- 650 _2
- $a mladý dospělý $7 D055815
- 655 _2
- $a časopisecké články $7 D016428
- 700 1_
- $a Klugerova, Michaela $u Department of Anthropology and Human Genetics, Faculty of Science, Charles University in Prague, Vinicna 7, 128 43 Prague, Czech Republic. Electronic address: Mickey.007@seznam.cz.
- 700 1_
- $a Vcelak, Josef $u Department of Molecular Endocrinology, Institute of Endocrinology, Narodni 8, 116 94 Prague, Czech Republic. Electronic address: jvcelak@endo.cz.
- 700 1_
- $a Baxova, Alice $u Institute of Biology and Medical Genetics, 1st Faculty of Medicine and General University Hospital, Charles University in Prague, Albertov 4, 128 00 Prague, Czech Republic. Electronic address: baxova@vfn.cz.
- 700 1_
- $a Kuklik, Miloslav $u Department of Molecular Endocrinology, Institute of Endocrinology, Narodni 8, 116 94 Prague, Czech Republic; Genetic Department Olsanska, 1st and 3rd Faculty of Medicine, Charles University in Prague, Olsanska 2666/7, 130 00 Prague, Czech Republic. Electronic address: honza.kuklik@volny.cz.
- 700 1_
- $a Vseticka, Jan $u Genetika Ostrava s.r.o., Korenskeho 1317/12, 702 00 Ostrava, Czech Republic. Electronic address: jan.vseticka55@gmail.com.
- 700 1_
- $a Beharka, Rastislav $u Department of Medical Genetics, University Hospital Brno, Cernopolni 212/9, 625 00 Brno, Czech Republic. Electronic address: rbeharka@fnbrno.cz.
- 700 1_
- $a Hirschfeldova, Katerina $u Institute of Biology and Medical Genetics, 1st Faculty of Medicine and General University Hospital, Charles University in Prague, Albertov 4, 128 00 Prague, Czech Republic. Electronic address: khirs@lf1.cuni.cz.
- 773 0_
- $w MED00009464 $t Clinica chimica acta; international journal of clinical chemistry $x 1873-3492 $g Roč. 464, č. - (2017), s. 30-36
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/27826100 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20170413 $b ABA008
- 991 __
- $a 20170427120118 $b ABA008
- 999 __
- $a ok $b bmc $g 1199879 $s 974192
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2017 $b 464 $c - $d 30-36 $e 20161105 $i 1873-3492 $m Clinica chimica acta $n Clin Chim Acta $x MED00009464
- LZP __
- $a Pubmed-20170413
