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Delineation of New Disorders and Phenotypic Expansion of Known Disorders Through Whole Exome Sequencing

  • Clinical Genetics (JM Stoler, Section Editor)
  • Published:
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Abstract

Whole-exome sequencing (WES) has revolutionized gene discovery in human disease, drastically improving detection of pathogenic variation, expanding the delineation of molecular networks, enriching characterization of genomic architecture and refining the genotype–endophenotype distinctions in heterogeneous phenotypes. WES studies, often aided by collaborative consortia, have proven particularly effective in identifying the genetic etiology of autism, epilepsy, neurodevelopmental disabilities, brain malformations, congenital heart disease, congenital diaphragmatic hernia, multiple congenital anomalies, rare diseases, and the extreme phenotypes of common diseases. Analysis of proband and parents with a trio design has proven effective in the identification of de novo events and their contribution to disease, extending analysis of sporadic conditions beyond prior studies using comparative genomic hybridization and chromosome microarrays. WES has demonstrable utility in the clinical setting with impactful diagnostic yield across many diseases and is increasingly being adopted for its unbiased, efficient, and accurate ability to investigate the basis of human disease.

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Acknowledgments

Joseph Picoraro is funded through NIH 5T32GM082771-05.

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Authors and Affiliations

  1. Department of Pediatrics, Columbia University Medical Center, 622 West 168th Street, PH17-105, New York, NY, 10032, USA

    Joseph A. Picoraro

  2. Department of Pediatrics, Columbia University Medical Center, 1150 St. Nicholas Avenue, New York, NY, 10032, USA

    Wendy K. Chung

  3. Department of Medicine, Columbia University Medical Center, New York, NY, USA

    Wendy K. Chung

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  1. Joseph A. Picoraro
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  2. Wendy K. Chung
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Correspondence to Wendy K. Chung.

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This article is part of the Topical Collection on Clinical Genetics.

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Picoraro, J.A., Chung, W.K. Delineation of New Disorders and Phenotypic Expansion of Known Disorders Through Whole Exome Sequencing. Curr Genet Med Rep 3, 209–218 (2015). https://doi.org/10.1007/s40142-015-0079-5

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