Khil, P.P. et al. Genome Res. advance online publication (24 February 2012).

Double-stranded breaks (DSBs) that occur in the DNA—for example, during recombination—can be mapped using chromatin immunoprecipitation followed by sequencing, but genome-wide mapping of these 'recombination hotspots' is challenging in mammalian cells in part because of a low frequency of the hotspots. Inspired by approaches used in yeast, Khil et al. incorporated single-stranded DNA (ssDNA) computational detection methods and an ssDNA-enrichment step based on the faster annealing time of ssDNA compared to double-stranded DNA to the standard chromatin immunoprecipitation–sequencing protocol. The method—ssDNA sequencing or SSDS—improved the sensitivity and specificity of meiotic DSB hotspot detection in mouse samples. The method can also be extended to other systems in which identification of ssDNA or DSBs is desired.