title: How next-generation sequencing is transforming complex disease genetics.
abstract: 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.
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva 1211, Switzerland.
authors.forename: Helena
authors.initials: H
authors.lastname: Kilpinen
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Barrett
mesh_terms: D030541:Databases, Genetic; D056726:Genetic Association Studies / Q000379:methods; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D023281:Genomics / Q000379:methods / Q000639:trends; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D016045:Human Genome Project; D006801:Humans; D015810:Linkage Disequilibrium