Genetic Analysis Workshop 17 (GAW17) was held on October 13-16, 2010, in Boston, Massachusetts. The focus of GAW17 was on methods and challenges of the analysis of next-generation sequence data using a mini-exome data set. Two different study designs were simulated, unrelated individuals and large families, each with the same sample size. GAW17 was attended by 274 participants from 19 countries. The 166 contributions were organized into 15 discussion groups of 5-13 articles each. This supplement to Genetic Epidemiology provides further details on GAW17, and primary findings are highlighted in the individual group summary articles. In addition, the supplement includes two methodological articles (one on statistical approaches for collapsing methods and one on machine learning methods) to give an overview of the methods that many of the workshop participants used. We conclude the supplement with a discussion of critical aspects in the analysis of next-generation sequencing data.