Surrendering to genomic noise – de novo mutations in schizophrenia

Heterogeneity. Family-based exome sequencing or trio exome sequencing for de novo mutations is currently the method of choice to identify genetic risk factors in neurodevelopmental disorders. However, given the increasingly recognized variability in the human genome, the hunt for causative de novo mutations is sometimes an uphill battle – it is impossible to distinguish causal mutations from random events unless genes are affected repeatedly. In a recent publication in Nature, Fromer and colleagues present the most comprehensive search for de novo mutations in schizophrenia to date. They observe an incredible genetic heterogeneity that reflects the genetic architecture of neurodevelopmental disorders. Continue reading

How a pathogenic de novo mutation in SCN1A ended up in the Exome Variant Server

The omics flood. Large amounts of sequence data are produced every day and we can use the genetic information of several thousand individuals as controls of any present-day genetic study. However, much of research on “traditional” epilepsy genes had been performed prior to the genomic era and often only included limited control cohorts. This begs the question whether a closer look at the currently available data might provide additional information. Now, a recent paper in the Journal of Neurogenetics investigates the presence of reported mutations for epilepsy in large, available datasets. And the results are surprising. Continue reading