Mutations of Pre-mRNA Splicing Regulatory Elements: Are
Predictions Moving Forward to Clinical Diagnostics?

J 2017

Mutations of Pre-mRNA Splicing Regulatory Elements: Are Predictions Moving Forward to Clinical Diagnostics?

GRODECKA, Lucie, Emanuele BURATTI and Tomáš FREIBERGER

Basic information

Original name

Mutations of Pre-mRNA Splicing Regulatory Elements: Are Predictions Moving Forward to Clinical Diagnostics?

Authors

GRODECKA, Lucie (203 Czech Republic), Emanuele BURATTI (380 Italy) and Tomáš FREIBERGER (203 Czech Republic, guarantor, belonging to the institution)

Edition

International Journal of Molecular Sciences, Basel, MDPI AG, 2017, 1422-0067

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10600 1.6 Biological sciences

Country of publisher

Switzerland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 3.687

RIV identification code

RIV/00216224:14740/17:00095667

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.3390/ijms18081668

UT WoS

000408897400069

Keywords in English

splicing regulatory elements; in silico predictions; pre-mRNA splicing; mutation; evaluation of prediction tools; variants of unknown significance; splicing aberration

Abstract

V originále

For more than three decades, researchers have known that consensus splice sites alone are not sufficient regulatory elements to provide complex splicing regulation. Other regulators, so-called splicing regulatory elements (SREs) are needed. Most importantly, their sequence variants often underlie the development of various human disorders. However, due to their variable location and high degeneracy, these regulatory sequences are also very difficult to recognize and predict. Many different approaches aiming to identify SREs have been tried, often leading to the development of in silico prediction tools. While these tools were initially expected to be helpful to identify splicing-affecting mutations in genetic diagnostics, we are still quite far from meeting this goal. In fact, most of these tools are not able to accurately discern the SRE-affecting pathological variants from those not affecting splicing. Nonetheless, several recent evaluations have given appealing results (namely for EX-SKIP, ESRseq and Hexplorer predictors). In this review, we aim to summarize the history of the different approaches to SRE prediction, and provide additional validation of these tools based on patients' clinical data. Finally, we evaluate their usefulness for diagnostic settings and discuss the challenges that have yet to be met.

Links

NV16-34414A, research and development project

Name: Určení genových oblastí náchylných ke vzniku mutací ovlivňujících sestřih mRNA

Citovat

GRODECKA, Lucie, Emanuele BURATTI and Tomáš FREIBERGER. Mutations of Pre-mRNA Splicing Regulatory Elements: Are Predictions Moving Forward to Clinical Diagnostics? International Journal of Molecular Sciences. Basel: MDPI AG, 2017, vol. 18, No 8, p. nestránkováno, 14 pp. ISSN 1422-0067. Available from: https://dx.doi.org/10.3390/ijms18081668.

@article{1393527,
   author = {Grodecka, Lucie and Buratti, Emanuele and Freiberger, Tomáš},
   article_location = {Basel},
   article_number = {8},
   doi = {http://dx.doi.org/10.3390/ijms18081668},
   keywords = {splicing regulatory elements; in silico predictions; pre-mRNA splicing; mutation; evaluation of prediction tools; variants of unknown significance; splicing aberration},
   language = {eng},
   issn = {1422-0067},
   journal = {International Journal of Molecular Sciences},
   title = {Mutations of Pre-mRNA Splicing Regulatory Elements: Are Predictions Moving Forward to Clinical Diagnostics?},
   url = {http://www.mdpi.com/1422-0067/18/8/1668},
   volume = {18},
   year = {2017}
}

TY  - JOUR
ID  - 1393527
AU  - Grodecka, Lucie - Buratti, Emanuele - Freiberger, Tomáš
PY  - 2017
TI  - Mutations of Pre-mRNA Splicing Regulatory Elements: Are Predictions Moving Forward to Clinical Diagnostics?
JF  - International Journal of Molecular Sciences
VL  - 18
IS  - 8
SP  - nestránkováno
EP  - nestránkováno
PB  - MDPI AG
SN  - 14220067
KW  - splicing regulatory elements
KW  - in silico predictions
KW  - pre-mRNA splicing
KW  - mutation
KW  - evaluation of prediction tools
KW  - variants of unknown significance
KW  - splicing aberration
UR  - http://www.mdpi.com/1422-0067/18/8/1668
L2  - http://www.mdpi.com/1422-0067/18/8/1668
N2  - For more than three decades, researchers have known that consensus splice sites alone are not sufficient regulatory elements to provide complex splicing regulation. Other regulators, so-called splicing regulatory elements (SREs) are needed. Most importantly, their sequence variants often underlie the development of various human disorders. However, due to their variable location and high degeneracy, these regulatory sequences are also very difficult to recognize and predict. Many different approaches aiming to identify SREs have been tried, often leading to the development of in silico prediction tools. While these tools were initially expected to be helpful to identify splicing-affecting mutations in genetic diagnostics, we are still quite far from meeting this goal. In fact, most of these tools are not able to accurately discern the SRE-affecting pathological variants from those not affecting splicing. Nonetheless, several recent evaluations have given appealing results (namely for EX-SKIP, ESRseq and Hexplorer predictors). In this review, we aim to summarize the history of the different approaches to SRE prediction, and provide additional validation of these tools based on patients' clinical data. Finally, we evaluate their usefulness for diagnostic settings and discuss the challenges that have yet to be met.
ER  -

GRODECKA, Lucie, Emanuele BURATTI and Tomáš FREIBERGER. Mutations of Pre-mRNA Splicing Regulatory Elements: Are Predictions Moving Forward to Clinical Diagnostics? \textit{International Journal of Molecular Sciences}. Basel: MDPI AG, 2017, vol.~18, No~8, p.~nestránkováno, 14 pp. ISSN~1422-0067. Available from: https://dx.doi.org/10.3390/ijms18081668.

Detailed Information on Publication Record