RNA splicing, genetic variation, and disease

By: James V. Kohl | Published on: April 29, 2016

More than 600 blog posts on this domain attest to the fact that nutrient energy-dependent RNA-mediated cell type differentiation is the key to healthy longevity in all living genera. Only those who have missed the accurate representations of others who have linked angstroms to ecosystems via the innate immune system, the physiology of reproduction, and supercoiled DNA will continue to place RNA splicing into the context of disease, without acknowledging that RNA splicing is the key to Precision Medicine.

RNA splicing is a primary link between genetic variation and disease


RNA splicing links genetics to disease

Many genetic variants associated with disease have no apparent effect on any specific protein coding sequence. Li et al. systematically analyzed the effects of DNA variants on the main steps of gene regulation, from the chromatin state through protein function. One-third of expression quantitative train loci (QTLs) are mediated through transcriptional processes, not chromatin. Splice QTLs and expression QTLs are about comparable in their complex disease risk. Posttranscriptional mechanisms therefore play a large role in translating genotype to phenotype.


Noncoding variants play a central role in the genetics of complex traits, but we still lack a full understanding of the molecular pathways through which they act. We quantified the contribution of cis-acting genetic effects at all major stages of gene regulation from chromatin to proteins, in Yoruba lymphoblastoid cell lines (LCLs). About ~65% of expression quantitative trait loci (eQTLs) have primary effects on chromatin, whereas the remaining eQTLs are enriched in transcribed regions. Using a novel method, we also detected 2893 splicing QTLs, most of which have little or no effect on gene-level expression. These splicing QTLs are major contributors to complex traits, roughly on a par with variants that affect gene expression levels. Our study provides a comprehensive view of the mechanisms linking genetic variation to variation in human gene regulation.

My comment: MicroRNA flanking sequences link energy-dependent changes in base pairs from hydrogen-atom transfer to the RNA-mediated amino acid substitutions that differentiate the cell types of all living genera. The microRNA/messenger RNA balance links metabolic networks to genetic networks via the innate immune system, the energy-dependent physiology of reproduction and supercoiled DNA. The supercoiled DNA protects all organized genomes from virus-driven energy theft and genomic entropy.
Substitution of ‘expression quantitative trait loci (eQTLs)’ in attempts to link RNA splicing only to disease is disingenuous and borders on the absurd given the publication history of Yoav Gilad and/or Jonathan Pritchard. Both of them should know better than to keep trying to support neo-Darwinian nonsense with wordplay in the context of what they portray as new revelations.
See: Epigenetic modifications are associated with inter-species gene expression variation in primates
See: Human adaptations to diet, subsistence, and ecoregion are due to subtle shifts in allele frequency

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