Papers of the week – DEPDC5, a “female protective model” and rescued KCNT1 mutations

In final week before our EuroEPINOMICS Bild1bioinformatics workshop in Leuven people get a little busy and start reading up on all sorts of things. Accordingly, this week’s papers come from all areas of genetics and life science, including three studies in Annals of Neurology on epilepsy genetics.

Extended spectrum of DEPDC5 mutations in epilepsy. This week both the groups of Leanne Dibbens and our group from the EuroEPINOMICS consortium published two separate papers in Annals of Neurology relating to DEPDC5 mutations in association with focal epilepsies. The Australian group identified patients with lesional and non-lesional epilepsies affected by DEPDC5 mutations. In contrast, our group could identify mutations associated with Rolandic epilepsy and other non-lesional childhood epilepsies.

Sex dependent mimicry in butterflies by a single gene. In a recent letter in Nature Kunte et al. show that a single gene controls whether or not a female swallowtail butterfly has wing patterns resembling those of a toxic species. The gene makes a protein that controls the activity of numerous other genes in insects.

The beautiful equation. In a recent study in Frontiers of Human Neuroscience Zeki and colleagues asked mathematicians to rate equations on a scale ranging from “ugly” to “beautiful” while lying inside a functional magnetic resonance imaging (fMRI) scanner. They demonstrate that the more beautiful an equation was to the mathematician, the more activity their brain showed in an area called the A1 field of the medial orbitofrontal cortex, as the experience of beauty derived from other sources.

Epigenetic inheritance – what do we know? In this week’s Nature News Feature Hughes discusses old and current studies about the inheritance of epigenetic marks and points out that the mechanisms remain a puzzle.

Epistasis in humans. Epistatic mutations have different effects in combination than individually. That epistasis affects complex traits has been increasingly hypothesized since the GWAS era. In a recent article in Nature Hemani and collaborators demonstrate for the first time that it is possible to identify and replicate epistasis in complex traits amongst common human variants.

A “Female Protective Model” in Neurodevelopmental Disorders. A study in the American Journal for Human Genetics by Jacquemont and coworkers suggests that females require more severe genetic alterations to become affected with  neurodevelopmental disorders than males. They demonstrate that females have an increased etiological burden unlinked to rare deleterious variants on the X chromosome.

Inverse comorbidity of certain cancers and Central Nervous System (CNS) disorders? In a recent PLOS Genetics article Ibáñez et al. perform several transcriptomic meta-analysis of cancer and CNS datasets and present molecular evidence for inverse comorbidity of these diseases. They point to specific genes and pathways characteristic for each class of disorder, which are deregulated in opposite directions in CNS disorders and cancers. This deregulation might increase and simultaneously lower risk for each class of disorders.

RNA editing. A-to-I editing is the main form of RNA editing in mammals. In the latest issue of Genome Research Bazak and colleagues analyze deep sequenced RNA-seq data and identify a larger than expected amount of editing sides affecting the majority of human genes. Because most sites exhibit editing at only at very low levels, the molecular effect needs to be explored further.

KCNT1 gain-of-function rescued by quinidine. Milligan and coworkers demonstrate in Annals of Neurology that epilepsy associated mutations in KCNT1 result in a gain of function. In addition they could show that exposure to quinidine significantly reduces this gain-of-function for all mutations studied, establishing avenues for a targeted therapy.