Genetics

This post covers Mkhikian and colleagues' 2011 Nature Communications study, which inverted the usual order of genetic work by screening biologically first and testing association last. It follows the N-glycan branching pathway and the L-PHA readout with the 15 to 20% threshold that sets the scale, the cytokine result where more Mgat1 produces less branching and the 250-fold affinity difference that explains it, the screen of MGAT1 exon 2 in 42 patients and the allelic expression data behind the haplotype, the enzyme kinetics that make the direction of effect conditional on substrate supply, the swainsonine blocking experiment that places vitamin D protection inside the branching pathway, and the association statistics run last, including interactions that hold despite CTLA-4 Thr17Ala having no point association at all.