Human Splicing Finder: an online bioinformatics tool to predict splicing signals

被引:2052
作者
Desmet, Francois-Olivier [1 ]
Hamroun, Dalil [1 ,2 ]
Lalande, Marine [1 ]
Collod-Beroud, Gwenaelle [1 ]
Claustres, Mireille [1 ,2 ,3 ]
Beroud, Christophe [1 ,2 ,3 ]
机构
[1] INSERM, U827, F-34000 Montpellier, France
[2] CHU Montpellier, Hop Arnaud Villeneuve, Mol Genet Lab, F-34000 Montpellier, France
[3] Univ Montpellier I, UFR Med, F-34000 Montpellier, France
关键词
BRANCH-POINT MUTATION; MARFAN-SYNDROME; NONSENSE MUTATION; FBN1; MUTATIONS; UNCLASSIFIED VARIANTS; HETERODUPLEX ANALYSIS; FIBRILLIN-1; GENE; SEQUENCE MOTIFS; DYSTROPHIN GENE; SITE MUTATION;
D O I
10.1093/nar/gkp215
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thousands of mutations are identified yearly. Although many directly affect protein expression, an increasing proportion of mutations is now believed to influence mRNA splicing. They mostly affect existing splice sites, but synonymous, non-synonymous or nonsense mutations can also create or disrupt splice sites or auxiliary cis-splicing sequences. To facilitate the analysis of the different mutations, we designed Human Splicing Finder (HSF), a tool to predict the effects of mutations on splicing signals or to identify splicing motifs in any human sequence. It contains all available matrices for auxiliary sequence prediction as well as new ones for binding sites of the 9G8 and Tra2- Serine-Arginine proteins and the hnRNP A1 ribonucleoprotein. We also developed new Position Weight Matrices to assess the strength of 5 and 3 splice sites and branch points. We evaluated HSF efficiency using a set of 83 intronic and 35 exonic mutations known to result in splicing defects. We showed that the mutation effect was correctly predicted in almost all cases. HSF could thus represent a valuable resource for research, diagnostic and therapeutic (e.g. therapeutic exon skipping) purposes as well as for global studies, such as the GEN2PHEN European Project or the Human Variome Project.
引用
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页数:14
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