March 2012
Volume 53, Issue 14
Free
ARVO Annual Meeting Abstract  |   March 2012
Clinical Diagnosis by Targeted Sequencing Using Personal Genome Machine
Author Affiliations & Notes
  • Xia wang
    Molecular and Human Genetics,
    Human Genome Sequencing Center,
    Baylor College of Medicine, Houston, Texas
  • Donna Muzny
    Molecular and Human Genetics,
    Human Genome Sequencing Center,
    Baylor College of Medicine, Houston, Texas
  • Robert K. Koenekoop
    McGill Ocular Genetics Laboratory, McGill University Health Centre, Montreal, Quebec, Canada
  • Yuanqing Wu
    Human Genome Sequencing Center,
    Baylor College of Medicine, Houston, Texas
  • Christian Buhay
    Human Genome Sequencing Center,
    Baylor College of Medicine, Houston, Texas
  • Hui Wang
    Molecular and Human Genetics,
    Human Genome Sequencing Center,
    Baylor College of Medicine, Houston, Texas
  • Irma Lopez
    McGill Ocular Genetics Laboratory, McGill University Health Centre, Montreal, Quebec, Canada
  • Min Wang
    Human Genome Sequencing Center,
    Baylor College of Medicine, Houston, Texas
  • Richard A. Gibbs
    Molecular and Human Genetics,
    Human Genome Sequencing Center,
    Baylor College of Medicine, Houston, Texas
  • Rui Chen
    Molecular and Human Genetics,
    Human Genome Sequencing Center,
    Baylor College of Medicine, Houston, Texas
  • Footnotes
    Commercial Relationships  Xia wang, None; Donna Muzny, None; Robert K. Koenekoop, None; Yuanqing Wu, None; Christian Buhay, None; Hui Wang, None; Irma Lopez, None; Min Wang, None; Richard A. Gibbs, None; Rui Chen, None
  • Footnotes
    Support  R01EY018571
Investigative Ophthalmology & Visual Science March 2012, Vol.53, 4568. doi:
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      Xia wang, Donna Muzny, Robert K. Koenekoop, Yuanqing Wu, Christian Buhay, Hui Wang, Irma Lopez, Min Wang, Richard A. Gibbs, Rui Chen; Clinical Diagnosis by Targeted Sequencing Using Personal Genome Machine. Invest. Ophthalmol. Vis. Sci. 2012;53(14):4568.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : The molecular mechanisms for human genetic disorders are complex and the genetic heterogeneity is widely observed. Therefore, accurate molecular diagnosis of such genetic diseases, coupled with clinical phenotype, is the first step toward personalized treatment. The use of next generation sequencing (NGS) technology has the potential to dramatically improve molecular diagnostics. To introduce NGS to clinics, the sequencing method needs to be accurate, robust, rapid, and cost effective. The recently released Personal Genome Machine (PGM) is aiming to achieve these goals.The goal of this study is to test the efficacy and potential utility of PGM platform in a clinical setting.

Methods: : Coupled with gene capture technology, genomic DNA from a well characterized hapmap sample as well as two patients with autosomal recessive retinitis pigmentosa (arRP) was sequenced on the PGM platform. Systematic evaluation of the data coverage and accuracy was performed using both SNP genotyping microarray as well as Sanger sequencing. Putative mutations were Sanger sequenced, tested for the segregation within families, and screened in controls.

Results: : High quality results have been obtained from the sequencing of a well characterized hapmap sample with 99.59% (1181/1185) overall accuracy. Compound heterozygous mutations have been identified for both patients in USH2A. The c.2276G>T missense mutation and c.2299delG deletion were previously reported in RP patients. c.457T>G is a novel missense mutation.

Conclusions: : This study represents the first reported human patient case diagnosed by the PGM platform and demonstrates the potential utility of the PGM platform in a clinical setting.

Keywords: clinical (human) or epidemiologic studies: systems/equipment/techniques • retinitis • gene mapping 
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