How next-generation sequencing is transforming complex disease genetics

Trends Genet. 2013 Jan;29(1):23-30. doi: 10.1016/j.tig.2012.10.001. Epub 2012 Oct 25.


Progress in understanding the genetics of human disease is closely tied to technological developments in DNA sequencing. Recently, next-generation technology has transformed the scale of sequencing; compared to the methods used in the Human Genome Project, modern sequencers are 50000-fold faster. Complex disease genetics presents an immediate opportunity to use this technology to move from approaches using only partial information (linkage and genome-wide association studies, GWAS) to complete analysis of the relationship between genomic variation and phenotype. We first describe sequence-based improvements to existing study designs, followed by prioritization of both samples and genomic regions to be sequenced, and then address the ultimate goal of analyzing thousands of whole-genome sequences. Finally, we discuss how the same technology will also fundamentally change the way we understand the biological mechanisms underlying disease associations discovered through sequencing.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Databases, Genetic
  • Genetic Association Studies / methods
  • Genetic Diseases, Inborn / genetics*
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Genomics / methods
  • Genomics / trends
  • High-Throughput Nucleotide Sequencing* / methods
  • Human Genome Project
  • Humans
  • Linkage Disequilibrium