Otto et al. describe a next generation sequencing strategy to identify mutations in 120 patients affected with a rare cystic kidney disease. The strategy employed involves pooling the DNA of 24 patients, amplyfiying the exons (376) of 18 implicated genes, and next-generation sequence analysis. The strategy is quite specific and successful, confirming 92% of mutations in a control set and identifying disease causing mutations in 30 patients (25%). The strategy is two orders of magnitude more cost-effective compared to standard sequencing techniques and bears potential for further up scaling the number of genes and samples to be analyzed in parallel. (By Dr. Edgar A Otto, http://jmg.bmj.com/content/early/2010/11/09/jmg.2010.082552.abstract?papetoc )