Features of 5'-splice-site efficiency derived from disease-causing mutations and comparative genomics

Roca, X., Olson, A. J., Rao, A. R., Enerly, E., Kristensen, V. N., Borresen-Dale, A. L., Andresen, B. S., Krainer, A. R., Sachidanandam, R. (January 2008) Features of 5'-splice-site efficiency derived from disease-causing mutations and comparative genomics. Genome Res, 18 (1). pp. 77-87.

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URL: http://www.ncbi.nlm.nih.gov/pubmed/18032726
DOI: 10.1101/gr.6859308

Abstract

Many human diseases, including Fanconi anemia, hemophilia B, neurofibromatosis, and phenylketonuria, can be caused by 5'-splice-site (5'ss) mutations that are not predicted to disrupt splicing, according to position weight matrices. By using comparative genomics, we identify pairwise dependencies between 5'ss nucleotides as a conserved feature of the entire set of 5'ss. These dependencies are also conserved in human-mouse pairs of orthologous 5'ss. Many disease-associated 5'ss mutations disrupt these dependencies, as can some human SNPs that appear to alter splicing. The consistency of the evidence signifies the relevance of this approach and suggests that 5'ss SNPs play a role in complex diseases.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > mutations
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > splice site
CSHL Authors:
Communities: CSHL labs > Krainer lab
Depositing User: Matt Covey
Date: January 2008
Date Deposited: 26 Feb 2013 20:39
Last Modified: 06 Nov 2017 17:17
PMCID: PMC2134769
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27527

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