Mutation analysis of TRPS1 gene including core promoter, 5 ' UTR, and 3 ' UTR regulatory sequences with insight into their organization
Popis výsledku
Identifikátory výsledku
Kód výsledku v IS VaVaI
Nalezeny alternativní kódy
RIV/00216208:11310/17:10362722 RIV/00064165:_____/17:10362722 RIV/65269705:_____/17:00075966
Výsledek na webu
DOI - Digital Object Identifier
Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Mutation analysis of TRPS1 gene including core promoter, 5 ' UTR, and 3 ' UTR regulatory sequences with insight into their organization
Popis výsledku v původním jazyce
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.
Název v anglickém jazyce
Mutation analysis of TRPS1 gene including core promoter, 5 ' UTR, and 3 ' UTR regulatory sequences with insight into their organization
Popis výsledku anglicky
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.
Klasifikace
Druh
Jimp - Článek v periodiku v databázi Web of Science
CEP obor
—
OECD FORD obor
10600 - Biological sciences
Návaznosti výsledku
Projekt
—
Návaznosti
V - Vyzkumna aktivita podporovana z jinych verejnych zdroju
Ostatní
Rok uplatnění
2017
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Údaje specifické pro druh výsledku
Název periodika
Clinica Chimica Acta
ISSN
0009-8981
e-ISSN
—
Svazek periodika
464
Číslo periodika v rámci svazku
January
Stát vydavatele periodika
NL - Nizozemsko
Počet stran výsledku
7
Strana od-do
30-36
Kód UT WoS článku
000393003600006
EID výsledku v databázi Scopus
2-s2.0-84994618787
Základní informace
Druh výsledku
Jimp - Článek v periodiku v databázi Web of Science
OECD FORD
Biological sciences
Rok uplatnění
2017