ElSharawy, A., Hundrieser, B., Brosch, M., Wittig, M., Huse, K., Platzer, M., Becker, A., Simon, M., Rosenstiel, Philip, Schreiber, Stefan, Krawczak, S. and Hampe, J. (2009) Systematic Evaluation of the Effect of Common SNPs on Pre-mRNA Splicing. Human Mutation, 30 (4). pp. 625-632. DOI 10.1002/humu.20906.

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Abstract

The evolutionary and biomedical importance of differential mRNA splicing is well established. Numerous studies have assessed patterns of differential splicing in different genes and correlated these patterns to the genotypes for adjacent single,nucleotide polymorphisms (SNPs). Here, We have chosen a reverse approach and screened dbSNP for common SNPs at either canonical splice sites or exonic splice enhancers (ESEs) that would be classified as putatively splicing-relevant by bioinformatic tools. The 223 candidate SNPs retrieved from dbSNP were experimentally tested using a previously established panel of 92 matching DNAs and cDNAs. For each SNP, 16 cDNAs providing a balanced representation of the genotypes at the respective SNP were investigated by nested RT-PCR and subsequent sequencing. Putative allele,dependent splicing was verified by the cloning of PCR products. The positive predictive value of the bioinformatics tools turned out to be low,, ranging from 0% for ESEfinder to 99% (in the case of acceptor-site SNPs) for a recently reported neural network. The results highlight the need for a better understanding of the sequence characteristics of functional splice-sites to improve our ability to predict in silico the splicing relevance of empirically observed DNA sequence variants. Hum Mutat 30, 625-632, 2009. (C) 2009 Wiley-Liss, Inc.

Document Type:	Article
Keywords:	snpalternative splicing snp-dependent splicing exonic splice enhancers base-pair substitutions human genes enhancers junctions mutation database disease exons consequences disruption
Research affiliation:	Kiel University Kiel University > Kiel Marine Science OceanRep > The Future Ocean - Cluster of Excellence
Refereed:	Yes
Open Access Journal?:	No
Publisher:	Wiley
Projects:	Future Ocean
Date Deposited:	11 Feb 2011 12:15
Last Modified:	23 Sep 2019 23:52
URI:	https://oceanrep.geomar.de/id/eprint/9363

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