Imagine an RNA molecule keeping company with an RNA editing enzyme, both inside a sealed box. If no observer is able to witness an editing event, will it ever really occur?

Lior Pachter (UC Berkeley) did not go quite so far as this Gedankenexperiment in teasing the audience at Cold Spring Harbor's Biology of Genomes 2012 conference, but did make the provocative claim that it may never be possible to call with certainty individual RNA editing events.

Uncertainty principles abounded in Debbie Nickerson's (University of Washington) invited presentation on exome sequencing: exomics has proved reasonably successful with Mendelian disorders, but will its application to complex traits – that she and others are now undertaking – pay off? Fellow speaker Mark McCarthy has calculated that 20k-30k exomes will be needed to achieve sufficient power for Type II Diabetes genetic association studies.

Nickerson's talk was an engaging meander through a career that has paralleled the evolution of genome biology research; part-history of science, part-autobiography (Barbara McClintock on how to handle science's alpha males: "Forget 'em!"), part-cutting edge genomics…and a puzzling slide featuring a gnome (cryptic depiction of a genome harboring a deleterious deletion?).

Nickerson emphasized the value of ensuring her exome sequencing data are readily available to other researchers, as she has done with the Exome Variant Server. This data sharing spirit was also apparent in a number of talks making use of 1000 Genomes, ENCODE or modENCODE datasets – clear evidence that large data collections are increasingly informing the discourse of genome biology, whatever one thinks about the cost effectiveness of "big science" data generation consortia.

While ENCODE and the like have sequenced DNA purified from vast numbers of cells, other presenters showed the potential of single cell sequencing as a new angle for characterizing processes such as meitoic recombination and tumor evolution. Elaine Mardis (WUSTL) and Paul Spellman (LBL) countered that high quality data and well thought out analytical approaches can also provide important insights into tumor evolution, and without the sample mass limitations of current single cell sequencing methods.

The meeting's talks spanned a pleasingly broad spectrum of topics – from shaggy dog stories (genetics of fur color) to assertions that reports of the Y chromosome's certain death have likely been exaggerated. The power of science as a tool to unravel the human story was impressively laid out by Jonathan Pritchard (University of Chicago), Jeff Kidd (University of Michigan) and Simon Myers (University of Oxford). Myers' sparkling exploration of the synergy between admixture traces and recorded history indulged and delighted the audience with some juicy Sherlock Holmes-cum-CSI "a-ha!" moments, by way of Genghis Khan and Alexander The Great – two alpha males that human geneticists would certainly be ill advised to forget.