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This article is part of the supplement: Beyond the Genome 2012

Open Access Oral presentation

Whole-genome sequencing and disease-gene detection

Lynn B Jorde

  • Correspondence: Lynn B Jorde

Author affiliations

Department of Human Genetics, University of Utah School of Medicine, UT, USA

Citation and License

BMC Proceedings 2012, 6(Suppl 6):O7  doi:10.1186/1753-6561-6-S6-O7

The electronic version of this article is the complete one and can be found online at:

Published:1 October 2012

© 2012 Jorde; licensee 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.

Oral presentation

Whole-genome sequencing (WGS) offers unique opportunities to identify rare variants that cause disease. We have developed a new software tool, VAAST (Variant Annotation, Analysis and Search Tool) that permits the identification of specific disease-causing mutations in WGS data. VAAST unambiguously identifies two disease-causing mutations in a family quartet in which both offspring have autosomal recessive primary ciliary dyskinesia and Miller syndrome. In addition, VAAST has identified a new X-linked progeria-like syndrome (Ogden syndrome) using exome data from two unrelated families. The mutation occurs in NAA10, which encodes an N-acetyltransferase needed for N-terminal acetylation of proteins. Functional studies demonstrate that the mutation causes a loss of function, and a genetic test has been developed for Ogden syndrome. We have also used VAAST to identify GATA4 as the cause of cardiac septal defects in a single four-generation pedigree. Using the Utah Population Database, we have identified a large multigenerational pedigree in which VAAST, combined with analysis of shared genome segments, identifies a new locus for Crohn disease. Finally, we present an application of VAAST in the identification of ATP1A3 as a causal gene for alternating hemiplegia of childhood.