Skip to main content


Volume 12 Supplement 1

Beyond the Genome 2011

  • Invited speaker presentation
  • Open Access

Next-generation human genetics

  • 1
Genome Biology201112 (Suppl 1) :I14

  • Published:


  • Genome Sequencing
  • Candidate Gene
  • Complex Disease
  • Analytical Strategy
  • Paradigm Shift

Over the past five years, a new generation of technologies has reduced the cost of DNA sequencing by more than four orders of magnitude, democratizing the field by putting the sequencing capacity of a major genome center in the hands of individual investigators [1]. To exploit this paradigm shift, we have developed new technical methods and analytical strategies for disease gene discovery based on whole exome and whole genome sequencing. Our results to date include proof of concept [2] and the first demonstration [3] that exome sequencing of a small number of individuals can be applied to solve Mendelian, single-gene, disorders such as Miller syndrome [3] and Kabuki syndrome [4]. Recently, we have also demonstrated that exome or genome sequencing of parent-child trios can be used to rapidly identify candidate genes for complex disorders such as autism [5]. We are currently extending these strategies to additional simple and complex diseases of unknown etiology.

Authors’ Affiliations

Department of Genome Sciences, University of Washington, Seattle, WA, USA


  1. Shendure J, Ji H: Next-generation DNA sequencing. Nat Biotechnol. 2008, 26: 1135-1145. 10.1038/nbt1486.PubMedView ArticleGoogle Scholar
  2. Ng SB, Turner EH, Robertson PD, Flygare SD, Bigham AW, Lee C, Shaffer T, Wong M, Bhattacharjee A, Eichler EE, Bamshad M, Nickerson DA, Shendure J: Targeted capture and massively parallel sequencing of 12 human exomes. Nature. 2009, 461: 272-276. 10.1038/nature08250.PubMedPubMed CentralView ArticleGoogle Scholar
  3. Ng SB, Buckingham KJ, Lee C, Bigham AW, Tabor HK, Dent KM, Huf CD, Shannon PT, Jabs EW, Nickerson DA, Shendure J, Bamshad MJ: Exome sequencing identifies the cause of a mendelian disorder. Nat Genet. 2010, 42: 30-35. 10.1038/ng.499.PubMedPubMed CentralView ArticleGoogle Scholar
  4. Ng SB, Bigham AW, Buckingham KJ, Hannibal MC, McMillin MJ, Gildersleeve HI, Beck AE, Tabor HK, Cooper GM, Mefford HC, Lee C, Turner EH, Smith JD, Rieder MJ, Yoshiura K, Matsumoto N, Ohta T, Niikawa N, Nickerson DA, Bamshad MJ, Shendure J: Exome sequencing identifies MLL2 mutations as a cause of Kabuki syndrome. Nat Genet. 2010, 42: 790-793. 10.1038/ng.646.PubMedPubMed CentralView ArticleGoogle Scholar
  5. O’Roak BJ, Deriziotis P, Lee C, Vives L, Schwartz JJ, Girirajan S, Karakoc E, Mackenzie AP, Ng SB, Baker C, Rieder MJ, Nickerson DA, Bernier R, Fisher SE, Shendure J, Eichler EE: Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations. Nat Genet. 2011, 43: 585-589. 10.1038/ng.835.PubMedPubMed CentralView ArticleGoogle Scholar


© Shendure; licensee BioMed Central Ltd. 2011

This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.