Mutation analysis of TRPS1 gene including core promoter, 5 ' UTR, and 3 ' UTR regulatory sequences with insight into their organization

Kód výsledku v IS VaVaI

RIV/65269705:_____/17:00075966 - isvavai.cz

Nalezeny alternativní kódy

RIV/00216208:11110/17:10362722 RIV/00216208:11310/17:10362722 RIV/00064165:_____/17:10362722

Výsledek na webu

https://www.sciencedirect.com/science/article/abs/pii/S0009898116304533?via%3Dihub

DOI - Digital Object Identifier

10.1016/j.cca.2016.11.007

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10603 - Genetics and heredity (medical genetics to be 3)

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2017

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Clinica Chimica Acta

ISSN

0009-8981

e-ISSN

—

Svazek periodika

464

Číslo periodika v rámci svazku

JAN

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