The human genome is way too complicated for me

What has become of that simple 21,000-gene genome of ours? Today even the definition of gene is no longer clear. What biotypes belong to lncRNAs and what’s the job of unitary pseudogenes? For geneticists dog-paddling in complex diseases another surprise came last year with the announcement that roughly 80% of the genome has some sort of function. Confused? Grab this issue of Genome Research and read the review by Mudge and colleagues, who discuss many examples of the transcriptional complexity within the human genome. Continue reading

“Meta-channelopathies” – RBFOX1 deletions and human epilepsy

Man is built to seize. When Hughlings Jackson made this famous comment pertaining to the inherent hyperexcitability of the human brain in response to a wide range of different stimuli, he probably didn’t anticipate the mechanisms of splicing regulation. Our CNS is actively protected from hyperexcitability through directed splicing of ion channel mRNA. Now, a recent study in Epilepsia finds that these mechanisms may be dysfunctional in human epilepsy. Continue reading

Seizures beget seizures through splicing in flies

The dynamic genome. Up to 95% of human genes undergo a process called alternative splicing. For these genes, several exons are present, which can be used alternatively or can be omitted. Accordingly, a single pre-mRNA can result in a variety of different proteins with different properties. For key players such as voltage-dependent sodium channels, it is therefore interesting to know which role alternative splicing plays in epilepsy. However, the splicing landscape of human sodium channels is complicated and difficult to investigate. Therefore, a model system is required where simple questions can be asked. A recent study now reveals interesting findings related to sodium channel splicing and seizure in the fruit fly.  Continue reading