Systematic analysis of splicing defects in selected primary immunodeficiencies-related genes
Jazyk angličtina Země Spojené státy americké Médium print-electronic
Typ dokumentu časopisecké články
PubMed
28359783
DOI
10.1016/j.clim.2017.03.010
PII: S1521-6616(16)30508-3
Knihovny.cz E-zdroje
- Klíčová slova
- Cryptic splice sites, Primary immunodeficiencies, Splicing prediction, Splicing-affecting variants,
- MeSH
- buňky Hep G2 MeSH
- dítě MeSH
- exony MeSH
- HeLa buňky MeSH
- inhibiční protein komplementu C1 MeSH
- kojenec MeSH
- komplement C1 - inaktivátory genetika MeSH
- lidé MeSH
- messenger RNA genetika MeSH
- mutace MeSH
- předškolní dítě MeSH
- protein Wiskottova-Aldrichova syndromu genetika MeSH
- proteinkinasa BTK MeSH
- receptory interleukinů - společná gama-podjednotka genetika MeSH
- rekombinantní fúzní proteiny genetika MeSH
- sestřih RNA * MeSH
- syndromy imunologické nedostatečnosti genetika MeSH
- transkripční faktor STAT3 genetika MeSH
- tyrosinkinasy genetika MeSH
- U937 buňky MeSH
- Check Tag
- dítě MeSH
- kojenec MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- BTK protein, human MeSH Prohlížeč
- CD40LIg fusion protein MeSH Prohlížeč
- IL2RG protein, human MeSH Prohlížeč
- inhibiční protein komplementu C1 MeSH
- komplement C1 - inaktivátory MeSH
- messenger RNA MeSH
- protein Wiskottova-Aldrichova syndromu MeSH
- proteinkinasa BTK MeSH
- receptory interleukinů - společná gama-podjednotka MeSH
- rekombinantní fúzní proteiny MeSH
- SERPING1 protein, human MeSH Prohlížeč
- STAT3 protein, human MeSH Prohlížeč
- transkripční faktor STAT3 MeSH
- tyrosinkinasy MeSH
- WAS protein, human MeSH Prohlížeč
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.
Citace poskytuje Crossref.org
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