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RNA splicing in human disease and in the clinic

RNA splicing in human disease and in the clinic
RNA splicing in human disease and in the clinic
Defects at the level of the pre-mRNA splicing process represent a major cause of human disease. Approximately 15–50% of all human disease mutations have been shown to alter functioning of basic and auxiliary splicing elements. These elements are required to ensure proper processing of pre-mRNA splicing molecules, with their disruption leading to misprocessing of the pre-mRNA molecule and disease. The splicing process is a complex process, with much still to be uncovered before we are able to accurately predict whether a reported genomic sequence variant (GV) represents a splicing-associated disease mutation or a harmless polymorphism. Furthermore, even when a mutation is correctly identified as affecting the splicing process, there still remains the difficulty of providing an exact evaluation of the potential impact on disease onset, severity and duration. In this review, we provide a brief overview of splicing diagnostic methodologies, from in silico bioinformatics approaches to wet lab in vitro and in vivo systems to evaluate splicing efficiencies. In particular, we provide an overview of how the latest developments in high-throughput sequencing can be applied to the clinic, and are already changing clinical approaches.
0143-5221
355-368
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Buratti, Emanuele
57e8e002-a8c2-409a-ac29-2fc4a1d1c8b9
Baralle, Diana
faac16e5-7928-4801-9811-8b3a9ea4bb91
Buratti, Emanuele
57e8e002-a8c2-409a-ac29-2fc4a1d1c8b9

Baralle, Diana and Buratti, Emanuele (2017) RNA splicing in human disease and in the clinic. Clinical Science, 131 (5), 355-368. (doi:10.1042/CS20160211).

Record type: Article

Abstract

Defects at the level of the pre-mRNA splicing process represent a major cause of human disease. Approximately 15–50% of all human disease mutations have been shown to alter functioning of basic and auxiliary splicing elements. These elements are required to ensure proper processing of pre-mRNA splicing molecules, with their disruption leading to misprocessing of the pre-mRNA molecule and disease. The splicing process is a complex process, with much still to be uncovered before we are able to accurately predict whether a reported genomic sequence variant (GV) represents a splicing-associated disease mutation or a harmless polymorphism. Furthermore, even when a mutation is correctly identified as affecting the splicing process, there still remains the difficulty of providing an exact evaluation of the potential impact on disease onset, severity and duration. In this review, we provide a brief overview of splicing diagnostic methodologies, from in silico bioinformatics approaches to wet lab in vitro and in vivo systems to evaluate splicing efficiencies. In particular, we provide an overview of how the latest developments in high-throughput sequencing can be applied to the clinic, and are already changing clinical approaches.

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More information

Accepted/In Press date: 15 December 2016
e-pub ahead of print date: 15 February 2017
Published date: 1 March 2017
Organisations: Human Development & Health

Identifiers

Local EPrints ID: 406368
URI: https://eprints.soton.ac.uk/id/eprint/406368
ISSN: 0143-5221
PURE UUID: ad0e6fe9-a64c-42e2-96e1-6e60d89f7a8e
ORCID for Diana Baralle: ORCID iD orcid.org/0000-0003-3217-4833

Catalogue record

Date deposited: 10 Mar 2017 10:45
Last modified: 18 May 2019 00:33

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