There is mounting evidence that some proportion of risk for a variety of common traits is due to rare, possibly more deleterious genetic variation. This is in contrast to the predominant viewpoint of the past several years in which common complex phenotypes were thought to result from fairly common genetic polymorphisms; this was referred to as the common disease – common variant hypothesis. The ability to consider the impact of rare variants has been aided by technological developments. The single most important technological development in studies of genetic disease in recent years is the revolutionary change in the way human sequence data are generated. Whereas genetic techniques were previously limited to genotyping specific markers, these new methodologies make it possible to generate “sequence” data, in other words, the actual sequence of nucleotides that make up an individual's DNA. Not surprisingly, this approach is fundamentally changing the way genetic disease studies are pursued. Moreover, despite the fact that sequencing an entire genome is still prohibitively expensive (i.e., ~$16,000 per individual), whole genome sequencing is set to become the standard as costs
