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Detection of clinically relevant exonic copy-number changes by array CGH

Authors

  • Philip M. Boone,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Carlos A. Bacino,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
    3. Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    4. Texas Children's Hospital, Houston, Texas
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  • Chad A. Shaw,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
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  • Patricia A. Eng,

    1. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
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  • Patricia M. Hixson,

    1. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
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  • Amber N. Pursley,

    1. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
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  • Sung-Hae L. Kang,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
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  • Yaping Yang,

    1. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
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  • Joanna Wiszniewska,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
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  • Beata A. Nowakowska,

    1. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
    Current affiliation:
    1. Center for Human Genetics, University Hospital, K.U. Leuven, Herestraat 49, 3000 Leuven, Belgium
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  • Daniela del Gaudio,

    1. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
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  • Zhilian Xia,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Gayle Simpson-Patel,

    1. Clinical Genetics, 'Specially for Children, Austin, Texas
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  • LaDonna L. Immken,

    1. Clinical Genetics, 'Specially for Children, Austin, Texas
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  • James B. Gibson,

    1. Clinical Genetics, 'Specially for Children, Austin, Texas
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  • Anne C.-H. Tsai,

    1. Department of Pediatrics, The Children's Hospital, University of Colorado School of Medicine, Aurora, Colorado
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  • Jennifer A. Bowers,

    1. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
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  • Tyler E. Reimschisel,

    1. Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
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  • Christian P. Schaaf,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
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  • Lorraine Potocki,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Texas Children's Hospital, Houston, Texas
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  • Fernando Scaglia,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    3. Texas Children's Hospital, Houston, Texas
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  • Tomasz Gambin,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Institute of Computer Science, Warsaw University of Technology, Warsaw, Poland
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  • Maciej Sykulski,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Institute of Informatics, Warsaw University, Warsaw, Poland
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  • Magdalena Bartnik,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland
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  • Katarzyna Derwinska,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland
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  • Barbara Wisniowiecka-Kowalnik,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland
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  • Seema R. Lalani,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
    3. Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    4. Texas Children's Hospital, Houston, Texas
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  • Frank J. Probst,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Texas Children's Hospital, Houston, Texas
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  • Weimin Bi,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
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  • Arthur L. Beaudet,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
    3. Department of Pediatrics, Baylor College of Medicine, Houston, Texas
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  • Ankita Patel,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
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  • James R. Lupski,

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
    3. Department of Pediatrics, Baylor College of Medicine, Houston, Texas
    4. Texas Children's Hospital, Houston, Texas
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  • Sau Wai Cheung,

    Corresponding author
    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
    • Department of Molecular & Human Genetics, Baylor College of Medicine, 1 Baylor Plaza, NAB 2015, Houston, TX 77030
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  • Pawel Stankiewicz

    1. Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas
    2. Medical Genetics Laboratories, Baylor College of Medicine, Houston, Texas
    3. Department of Medical Genetics, Institute of Mother and Child, Warsaw, Poland
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  • Communicated by Michael Dean

Abstract

Array comparative genomic hybridization (aCGH) is a powerful tool for the molecular elucidation and diagnosis of disorders resulting from genomic copy-number variation (CNV). However, intragenic deletions or duplications—those including genomic intervals of a size smaller than a gene—have remained beyond the detection limit of most clinical aCGH analyses. Increasing array probe number improves genomic resolution, although higher cost may limit implementation, and enhanced detection of benign CNV can confound clinical interpretation. We designed an array with exonic coverage of selected disease and candidate genes and used it clinically to identify losses or gains throughout the genome involving at least one exon and as small as several hundred base pairs in size. In some patients, the detected copy-number change occurs within a gene known to be causative of the observed clinical phenotype, demonstrating the ability of this array to detect clinically relevant CNVs with subkilobase resolution. In summary, we demonstrate the utility of a custom-designed, exon-targeted oligonucleotide array to detect intragenic copy-number changes in patients with various clinical phenotypes. Hum Mutat 31:1–17, 2010. © 2010 Wiley-Liss, Inc.

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