A catalog of DNA polymorphism present in natural populations is fundamental to population and quantitative genetic analysis. From chromosome banding patterns to allozyme variation, each new technological development has produced insight into patterns and levels of DNA sequencing variation. Taking advantage of the latest advances in DNA sequencing technology, we are using genome sequences of ~50 strains of S. cerevisiae to systematically catalog various types of DNA polymorphism, including chromosome rearrangements and other structural variation, insertion and deletion polymorphism and single nucleotide polymorphism. The development of bioinformatic tools and computational methods is an essential component of analyzing genome polymorphism data in yeast, humans and other organisms.