Single-nucleotide polymorphisms in NAGNAG acceptors are highly predictive for variations of alternative splicing
Open accessAbstract
Aberrant or modified splicing patterns of genes are causative for many human diseases. Therefore, the identification of genetic variations that cause changes in the splicing pattern of a gene is important. Elsewhere, we described the widespread occurrence of alternative splicing at NAGNAG acceptors. Here, we report a genomewide screen for single-nucleotide polymorphisms (SNPs) that affect such tandem acceptors. From 121 SNPs identified, we extracted 64 SNPs that most likely affect alternative NAGNAG splicing. We demonstrate that the NAGNAG motif is necessary and sufficient for this type of alternative splicing. The evolutionarily young NAGNAG alleles, as determined by the comparison with the chimpanzee genome, exhibit the same biases toward intron phase 1 and single-amino acid insertion/deletions that were already observed for all human NAGNAG acceptors. Since 28% of the NAGNAG SNPs occur in known disease genes, they represent preferable candidates for a more-detailed functional analysis, especially since the splice relevance for some of the coding SNPs is overlooked. Against the background of a general lack of methods for identifying splice-relevant SNPs, the presented approach is highly effective in the prediction of polymorphisms that are causal for variations in alternative splicing.
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The protective allele results in a non-synonymous glycine to arginine change at amino acid position 523 and has also been implicated in alternate splicing.
“The protective allele results in a non-synonymous glycine to arginine change at amino acid position 523 and has also been implicated in alternate splicing (38), both of which offer a starting point for investigation of the impact of this variation on gene function.”
From Individual common variants exert weak effects on the risk for autism spectrum disorders (2012) · cites this paper as [38]
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- Authors
- Hiller, M., Huse, K., Szafranski, K., Jahn, N., Hampe, J., Schreiber, S., Backofen, R., & Platzer, M.
- Affiliations
- Friedrich Schiller University Jena (DE)
- Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) (DE)
- Christian-Albrechts-Universität zu Kiel (DE)
- Corresponding author
- Platzer, Matthias
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2006-02
- Volume
- 78
- Issue
- 2
- Pages
- 291-302
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1380236
- OpenAlex
- W1977343146
- Cited by
- 54
- References
- 25
- Citations by year
- 2023: 1 · 2022: 2 · 2020: 3 · 2019: 1 · 2017: 1 · 2015: 3 · 2014: 2 · 2013: 3 · 2012: 4
- FWCI
- 3.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Informationszentrum Lebenswissenschaften (ZB MED) (submittedVersion)
- Funders
- Bundesministerium für Bildung und Forschung (01GR0105, 01GS0426, 0312704E)
- Deutsche Forschungsgemeinschaft (SFB604-02)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- alternative splicing, single nucleotide polymorphisms, splice site prediction, intron phase, indels, disease-associated genes, splice variants
- MeSH terms
- Alleles, Animals, Base Sequence, Pan troglodytes, Humans, Molecular Sequence Data, Genome, Human, Alternative Splicing, Sequence Analysis, DNA, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, RNA Splice Sites
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