ArticlePLoS biology2004
Single nucleotide polymorphism-based validation of exonic splicing enhancers.
Article in PLoS biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 1 of them a synthesis that pooled it.
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Who cites it
108 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Associations between two genetic variants in NKX2-5 and risk of congenital heart disease in Chinese population: a meta-analysis.PloS one · 2013Pooled it
- Protocol for Designing and Interpreting Minigene Assays to Validate Candidate Splice-Altering Variants Using Long-read Sequencing.Current protocols · 2026Article
- Selection on synonymous sites: the unwanted transcript hypothesis.Nature reviews. Genetics · 2024Review
- In rice splice variants that restore the reading frame after frameshifting indel introduction are common, often induced by the indels and sometimes lead to organism-level rescue.PLoS genetics · 2022Article
- Evidence in disease and non-disease contexts that nonsense mutations cause altered splicing via motif disruption.Nucleic acids research · 2021Article
- Article
- The etiology of Down syndrome: Maternal MCM9 polymorphisms increase risk of reduced recombination and nondisjunction of chromosome 21 during meiosis I within oocyte.PLoS genetics · 2021Article
- A Depletion of Stop Codons in lincRNA is Owing to Transfer of Selective Constraint from Coding Sequences.Molecular biology and evolution · 2020Article
- Genome-wide analysis reveals the association between alternative splicing and DNA methylation across human solid tumors.BMC medical genomics · 2020Article
- Splicing of long non-coding RNAs primarily depends on polypyrimidine tract and 5' splice-site sequences due to weak interactions with SR proteins.Nucleic acids research · 2019Article
- Exonic CLDN16 mutations associated with familial hypomagnesemia with hypercalciuria and nephrocalcinosis can induce deleterious mRNA alterations.BMC medical genetics · 2019Article
- Exonic splice regulation imposes strong selection at synonymous sites.Genome research · 2018Article
- Refining the Ambush Hypothesis: Evidence That GC- and AT-Rich Bacteria Employ Different Frameshift Defence Strategies.Genome biology and evolution · 2018Article
- Identification of Eight Spliceogenic Variants in BRCA2 Exon 16 by Minigene Assays.Frontiers in genetics · 2018Article
- Saturation mutagenesis reveals manifold determinants of exon definition.Genome research · 2018Article
- Adenine Enrichment at the Fourth CDS Residue in Bacterial Genes Is Consistent with Error Proofing for +1 Frameshifts.Molecular biology and evolution · 2017Article
- Depletion of somatic mutations in splicing-associated sequences in cancer genomes.Genome biology · 2017Article
- Estimating the prevalence of functional exonic splice regulatory information.Human genetics · 2017Review
- The association of lipid metabolism relative gene polymorphisms and ischemic stroke in Han and Uighur population of Xinjiang.Lipids in health and disease · 2017Article
- Both Maintenance and Avoidance of RNA-Binding Protein Interactions Constrain Coding Sequence Evolution.Molecular biology and evolution · 2017Article
48 more citing papers are in PubMed but not listed here.
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4 authors.
Funding
Abstract
Because deleterious alleles arising from mutation are filtered by natural selection, mutations that create such alleles will be underrepresented in the set of common genetic variation existing in a population at any given time. Here, we describe an approach based on this idea called VERIFY (variant elimination reinforces functionality), which can be used to assess the extent of natural selection acting on an oligonucleotide motif or set of motifs predicted to have biological activity. As an application of this approach, we analyzed a set of 238 hexanucleotides previously predicted to have exonic splicing enhancer (ESE) activity in human exons using the relative enhancer and silencer classification by unanimous enrichment (RESCUE)-ESE method. Aligning the single nucleotide polymorphisms (SNPs) from the public human SNP database to the chimpanzee genome allowed inference of the direction of the mutations that created present-day SNPs. Analyzing the set of SNPs that overlap RESCUE-ESE hexamers, we conclude that nearly one-fifth of the mutations that disrupt predicted ESEs have been eliminated by natural selection (odds ratio = 0.82 +/- 0.05). This selection is strongest for the predicted ESEs that are located near splice sites. Our results demonstrate a novel approach for quantifying the extent of natural selection acting on candidate functional motifs and also suggest certain features of mutations/SNPs, such as proximity to the splice site and disruption or alteration of predicted ESEs, that should be useful in identifying variants that might cause a biological phenotype.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.