Risk-associated coding synonymous SNPs in type 2 diabetes and neurodegenerative diseases: genetic silence and the underrated association with splicing regulation and epigenetics

Mutation Research
Maria KarambatakiSofia Kouidou

Abstract

Single nucleotide polymorphisms (SNPs) are tentatively critical with regard to disease predisposition, but coding synonymous SNPs (sSNPs) are generally considered "neutral". Nevertheless, sSNPs in serine/arginine-rich (SR) and splice-site (SS) exonic splicing enhancers (ESEs) or in exonic CpG methylation targets, could be decisive for splicing, particularly in aging-related conditions, where mis-splicing is frequently observed. We presently identified 33 genes T2D-related and 28 related to neurodegenerative diseases, by investigating the impact of the corresponding coding sSNPs on splicing and using gene ontology data and computational tools. Potentially critical (prominent) sSNPs comply with the following criteria: changing the splicing potential of prominent SR-ESEs or of significant SS-ESEs by >1.5 units (Δscore), or formation/deletion of ESEs with maximum splicing score. We also noted the formation/disruption of CpGs (tentative methylation sites of epigenetic sSNPs). All disease association studies involving sSNPs are also reported. Only 21/670 coding SNPs, mostly epigenetic, reported in 33 T2D-related genes, were found to be prominent coding synonymous. No prominent sSNPs have been recorded in three key T2D-related genes (...Continue Reading

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Citations

Feb 2, 2019·BMC Medical Genomics·Seonggyun HanUNKNOWN for Alzheimer’s Disease Neuroimaging Initiative
May 14, 2019·Nucleosides, Nucleotides & Nucleic Acids·Khue Vu Nguyen
Mar 20, 2018·Alternatives to Laboratory Animals : ATLA·Zeeshan AliJohn J Pippin
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