This week, the University of Washington's Jay Shendure serves as a Genome Biology guest editor for the journal's special issue on exome sequencing. In an editorial, Shendure discusses the challenges and opportunities of the field, saying that while "exome sequencing fails to solve a substantial proportion of presumably Mendelian phenotypes, even in model organisms where the genetics are crystal clear," he says that "we are only a few years into an incredible trajectory in which exome sequencing and genome sequencing are reshaping the landscape of human genetics."
Elsewhere in the journal's exome sequencing section, investigators at the Radboud University Nijmegen Medical Centre review how they say "exome sequencing is revolutionizing Mendelian disease gene identification." In its paper, the Netherlands-based team discusses lessons learned during the last two years of exome sequencing experiments, opportunities for advancing clinical diagnoses using the technique, and future research directions toward "the role of de novo mutations in rare and common disorders," as well as to how "different mutations in the same gene can result in completely different phenotypes." Overall, the Radboud group says exome sequencing "is crucial for drawing accurate genotype-phenotype correlations and will undoubtedly improve diagnosis for the millions of individuals with Mendelian disease, improve family counseling and reveal new therapeutic targets."
The National Human Genome Research Institute's Leslie Biesecker, Duke University School of Medicine's Kevin Shianna, and NHGRI's Jim Mullikin this week speak to how exome sequencing has contributed "to our understanding of the dynamic nature of the genome," as well as the extent to which the technique's uptake has "been driven by cost alone," and whether the approach has "a limited 'shelf life.'"
Also this week, UW's Joshua Akey et al. discuss in Genome Biology "the promise and limitations of population exomics for human evolution studies." The team explores caveats of population exomics, including the prevalence of copy-number variation, "missing data," difficulties merging data sets, that "even with a low overall error rather, the sheer size of the exome means that false positives are inevitable," and, of course, that "exomes provide no information about non-coding regions, including many functionally important noncoding sites." Still, Akey and his colleagues say that exome sequencing "provides a powerful tool for population geneticists that will facilitate estimates of numerous evolutionary parameters with much greater precision than was previously possible."