Systematic analysis of splicing defects in selected primary immunodeficiencies-related genes

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00209775%3A_____%2F17%3AN0000009" target="_blank" >RIV/00209775:_____/17:N0000009 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14740/17:00095654

Výsledek na webu

<a href="https://www.journals.elsevier.com/clinical-immunology/" target="_blank" >https://www.journals.elsevier.com/clinical-immunology/</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/doi.org/10.1016/j.clim.2017.03.010" target="_blank" >doi.org/10.1016/j.clim.2017.03.010</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Systematic analysis of splicing defects in selected primary immunodeficiencies-related genes

Popis výsledku v původním jazyce

Both variants affecting splice sites and those in splicing regulatory elements (SREs) can impair pre-mRNA splicing, eventually leading to severe diseases. Despite the availability of many prediction tools, prognosis of splicing affection is not trivial, especially when SREs are involved. Here, we present data on 92 in silico-/55 minigene-analysed variants detected in genes responsible for the primary immunodeficiencies development (namely BTK, CD40LG, IL2RG, SERPING1, STAT3, and WAS). Of 20 splicing-affecting variants, 16 affected splice site while 4 disrupted potential SRE. The presence or absence of splicing defects was confirmed in 30 of 32 blood-derived patients' RNAs. Testing prediction tools performance, splice site disruptions and creations were reliably predicted in contrast to SRE-affecting variants for which just ESRseq, ΔHZEI-scores and EX-SKIP predictions showed promising results. Next, we found an interesting pattern in cryptic splice site predictions. These results might help PID-diagnosticians and geneticists cope with potential splicing-affecting variants.

Název v anglickém jazyce

Systematic analysis of splicing defects in selected primary immunodeficiencies-related genes

Popis výsledku anglicky

Both variants affecting splice sites and those in splicing regulatory elements (SREs) can impair pre-mRNA splicing, eventually leading to severe diseases. Despite the availability of many prediction tools, prognosis of splicing affection is not trivial, especially when SREs are involved. Here, we present data on 92 in silico-/55 minigene-analysed variants detected in genes responsible for the primary immunodeficiencies development (namely BTK, CD40LG, IL2RG, SERPING1, STAT3, and WAS). Of 20 splicing-affecting variants, 16 affected splice site while 4 disrupted potential SRE. The presence or absence of splicing defects was confirmed in 30 of 32 blood-derived patients' RNAs. Testing prediction tools performance, splice site disruptions and creations were reliably predicted in contrast to SRE-affecting variants for which just ESRseq, ΔHZEI-scores and EX-SKIP predictions showed promising results. Next, we found an interesting pattern in cryptic splice site predictions. These results might help PID-diagnosticians and geneticists cope with potential splicing-affecting variants.

Druh

J_ost - Ostatní články v recenzovaných periodicích

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

<a href="/cs/project/NV16-34414A" target="_blank" >NV16-34414A: Určení genových oblastí náchylných ke vzniku mutací ovlivňujících sestřih mRNA</a><br>

Návaznosti

V - Vyzkumna aktivita podporovana z jinych verejnych zdroju

Rok uplatnění

2017

Kód důvěrnosti údajů

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

Název periodika

Clinical Immunology

ISSN

1521-6616

e-ISSN

—

Svazek periodika

180

Číslo periodika v rámci svazku

July

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

12

Strana od-do

33-44

Kód UT WoS článku

000403998600005

EID výsledku v databázi Scopus

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