Ode to the humble Southern blot in the era of exomes

Methods to perform the Southern blot, the separation of pieces of DNA by size and then identification with a molecular probe, were first published in 1975,1 before some of us in academic medicine had even entered preschool. It seems astonishing in this post–Human Genome Project era that the technique still has relevance in modern genetic diagnostics. Yet, even with the growing availability of exome sequencing, the Southern blot remains the method of choice to detect expansions in nucleotide repeats in the human genome. In this issue of Neurology® Clinical Practice , Wallace and Bird2 remind us that neurologists forget this at our peril.