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Do SNPs prove exonic splicing enhancers are real?

Human polymorphism patterns validate computationally predicted ESEs and show splicing constrains exon evolution.

Source

Single nucleotide polymorphism-based validation of exonic splicing enhancers

Fairbrother WG, Holste D, Burge CB, et al. · PLoS biology · 2004

doi.org/10.1371/journal.pbio.0020268Read the full paper ↗155 citationscc by

What they did

Mapped common SNPs onto exons relative to RESCUE-ESE motifs and splice-site proximity, comparing natural vs simulated mutations.

What they found

ESE disruption and near-splice positions show signatures consistent with purifying selection; splicing constrains human exon evolution.

The limits

What it doesn't show

Does not experimentally assay every predicted hexamer in every tissue.

Key terms

ESE
Exonic splicing enhancer motif aiding exon recognition
SNP
Common single-nucleotide polymorphism
RESCUE-ESE
Computational method predicting ESEs
Purifying selection
Removal of deleterious alleles

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ESEs enhance

Common questions

What are ESEs?

Short sequences enhancing splicing

Key constraint?

Splicing shapes exon evolution

Useful features?

Splice proximity and ESE disruption

Data?

Human dbSNP / exons

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