Uncovering the roles of rare variants in common disease through whole-genome sequencing

Nat Rev Genet. 2010 Jun;11(6):415-25. doi: 10.1038/nrg2779.


Although genome-wide association (GWA) studies for common variants have thus far succeeded in explaining only a modest fraction of the genetic components of human common diseases, recent advances in next-generation sequencing technologies could rapidly facilitate substantial progress. This outcome is expected if much of the missing genetic control is due to gene variants that are too rare to be picked up by GWA studies and have relatively large effects on risk. Here, we evaluate the evidence for an important role of rare gene variants of major effect in common diseases and outline discovery strategies for their identification.

Publication types

  • Review

MeSH terms

  • Animals
  • Chromosome Mapping / methods
  • Disease / genetics*
  • Genetic Predisposition to Disease / genetics
  • Genetic Variation / physiology*
  • Genome-Wide Association Study / methods*
  • Humans
  • Models, Biological
  • Pedigree
  • Sequence Analysis, DNA / methods*