ArticleMolecular biology and evolution2016
Determinants of the Usage of Splice-Associated cis-Motifs Predict the Distribution of Human Pathogenic SNPs.
Article in Molecular biology and evolution, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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32 citing papers in PubMed, 40 citations in OpenAlex.
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- RNA Modification-Related Genetic Variants in Genomic Loci Associated with Bone Mineral Density and Fracture.Genes · 2022Article
- N6-methyladenosine-related single-nucleotide polymorphism analyses identify oncogene RNFT2 in bladder cancer.Cancer cell international · 2022Article
- RNA modification-related variants in genomic loci associated with body mass index.Human genomics · 2022Article
- A genome-wide association analysis: m6A-SNP related to the onset of oral ulcers.Frontiers in immunology · 2022Article
- Evidence in disease and non-disease contexts that nonsense mutations cause altered splicing via motif disruption.Nucleic acids research · 2021Article
- Classifying single nucleotide polymorphisms in humans.Molecular genetics and genomics : MGG · 2021Article
- RMDisease: a database of genetic variants that affect RNA modifications, with implications for epitranscriptome pathogenesis.Nucleic acids research · 2021Article
- Association of Vitamin D Metabolism Gene Polymorphisms with Autoimmunity: Evidence in Population Genetic Studies.International journal of molecular sciences · 2020Review
- Role of m6A RNA methylation in cardiovascular disease (Review).International journal of molecular medicine · 2020Review
- Integration Analysis of mFrontiers in genetics · 2020Article
- Examination of the associations between mHypertension research : official journal of the Japanese Society of Hypertension · 2019Article
- Genome-wide enrichment of mThe pharmacogenomics journal · 2019Article
- The Role of p.Ser1105Ser (inMedicina (Kaunas, Lithuania) · 2019Article
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2 authors at 1 institution in 1 country.
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Abstract
Where in genes do pathogenic mutations tend to occur and does this provide clues as to the possible underlying mechanisms by which single nucleotide polymorphisms (SNPs) cause disease? As splice-disrupting mutations tend to occur predominantly at exon ends, known also to be hot spots of cis-exonic splice control elements, we examine the relationship between the relative density of such exonic cis-motifs and pathogenic SNPs. In particular, we focus on the intragene distribution of exonic splicing enhancers (ESE) and the covariance between them and disease-associated SNPs. In addition to showing that disease-causing genes tend to be genes with a high intron density, consistent with missplicing, five factors established as trends in ESE usage, are considered: relative position in exons, relative position in genes, flanking intron size, splice sites usage, and phase. We find that more than 76% of pathogenic SNPs are within 3-69 bp of exon ends where ESEs generally reside, this being 13% more than expected. Overall from enrichment of pathogenic SNPs at exon ends, we estimate that approximately 20-45% of SNPs affect splicing. Importantly, we find that within genes pathogenic SNPs tend to occur in splicing-relevant regions with low ESE density: they are found to occur preferentially in the terminal half of genes, in exons flanked by short introns and at the ends of phase (0,0) exons with 3' non-"AGgt" splice site. We suggest the concept of the "fragile" exon, one home to pathogenic SNPs owing to its vulnerability to splice disruption owing to low ESE density.
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