Automagical disruption of an eQTL (1)

By: James V. Kohl | Published on: July 18, 2017

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E Kaitlynn Allen et al, SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans, Nature Medicine (2017). DOI: 10.1038/nm.4370

We prioritized SNPs in IFITM3 on the basis of putative biological function and identified rs34481144 in the 5′ UTR. We found evidence of a new association of rs34481144 with severe influenza in three influenza-infected cohorts characterized by different levels of influenza illness severity. We determined a role for rs34481144 as an expression quantitative trait locus (eQTL) for IFITM3, with the risk allele associated with lower mRNA expression.

My summary:

In the context of influenza and genetics, food energy-dependent changes in base pairs are linked to protection from influenza and constraint breaking mutations are linked to increased pathogenesis. The changes are reported in the context of an expression quantitative trait locus (eQTL) and promoters.

The authors ignore what is known about how quantized energy must be linked from natural selection for energy-dependent codon optimality to changes in the microRNA/messenger RNA balance. For example, energy-dependent changes link codon optimality from the physiology of pheromone-controlled reproduction to fixation of RNA-mediated amino acid substitutions in supercoiled DNA. Supercoiled DNA protects all organized genomes from the virus-driven degradation of messenger RNA and genomic entropy.

For comparison to the pseudoscientific nonsense still touted by theorists using mathematical models, see: “It’s all about that base.” If you do not understand why all serious scientists are laughing at pseudoscientists, learn how energy-dependent RNA-mediated cell type differentiation occurs.

All About that Base (Meghan Trainor Parody) 10 Dec 2014

SNP-mediated disruption of CTCF binding at the IFITM3 promoter is associated with risk of severe influenza in humans was reported as: Newly identified genetic marker may help detect high-risk flu patients

IFITM3 is an anti-viral protein that helps to block flu infection of lung cells and to promote survival of the killer T cells that help clear flu infection in the airways. Previous research from other scientists had reported an association between another IFITM3 variant (rs12252) and flu severity in Han Chinese patients. The underlying mechanism has remained unclear, and the rs12252 variant is rare in individuals of European ancestry.

“While this research focused on flu infections, the mechanism we identified has implications for regulating many genes involved in anti-viral activity,” Thomas said. “CTCF has gained prominence in recent years as a master regulator of genomic organization. Evidence in this study suggests the high-risk variant we identified may be part of a larger network of CTCF binding sites involved in regulation in other genes with anti-viral activity.”

A board game taking place inside a human cell! Players compete to build enzymes, hormones and receptors and fend off attacking Viruses!

See: Automagical disruption of an eQTL (2)