Nordström, K.J.V. et al. Nat. Biotechnol. 31, 325–330 (2013).

The field of genetics was founded on the principle of 'break it and find out what went wrong'. Mutation mapping—finding out what went wrong—has historically been the difficult part of genetic screening. Mapping by recombination-based methods is, happily, being replaced by faster methods that compare whole genome sequences, but these approaches rely on resequencing a reference genome. Nordström et al. avoid the need for a reference by finding changes in overlapping subsequences of sequence reads, known as k-mers, that are uniquely present in an affected individual and absent in an unaffected close relative. Their 'needle in the k-stack' (NIKS) algorithm identified candidate homozygous mutations in genetic screens of rice cultivars and alpine rockcresses. Examining backcrossed mutants allowed the authors to unambiguously identify causal mutations in nonrepetitive regions of the genome.