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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: http://www.biomedcentral.com/1753-6561/6/S6/O7


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 (http://creativecommons.org/licenses/by/2.0), 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.