S.B. Ng et al., “Exome sequencing identifies the cause of a Mendelian disorder,” Nat Genet, 42:30–35, 2009. (ID: 1600956)
Tracking down the genetic cause of inherited diseases is time consuming and expensive. But Jay Shendure of the University of Washington’s Department of Genome Sciences found a way to make it a whole lot easier. Instead of looking for problem genes by sequencing the full genome, Shendure’s lab sequenced only the exome—the protein-coding regions of the genome, including the exon boundaries—of patients. In the process, he found the gene that causes Miller syndrome.
Sequencing and analyzing the exome makes economic sense: it’s only 1% of the full genome. With the right software tools—and just a little bit of luck—you only need to study a small number of individuals. Shendure’s lab had shown that the idea worked last year when it verified the gene responsible for a disease with a known genetic mutation (Nature, 461:272–76, 2009).
Shendure says that the experimental part of the project took one graduate student, Sarah Ng, “a few months and one sequencing instrument.” Sequencing unrelated individuals, and control exomes with the same platform and method, were critical to their success.
F1000 member Richard Wintle, from the Centre for Applied Genomics in Toronto, writes in his review that whole-exome sequencing will be “of great value in the identification of genes for rare disorders and,” he writes, “holds great promise for gene discovery even in more common conditions.”
F1000 evaluators: R. F. Wintle and S. Scherer (Univ. of Toronto) • S. Salzberg (Univ. of Maryland) • M. Ramsay (Univ. of the Witwatersrand)
Visit the complete F1000 review of this paper.