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High-Resolution Survey in Familial Parkinson Disease Genes Reveals Multiple Independent Copy Number Variation Events in PARK2

Authors

  • Liyong Wang,

    Corresponding author
    1. John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida
    2. Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida
    • Correspondence to: Liyong Wang, University of Miami, 1501 NW 10th Ave, BRB 609, Miami, FL 33136, USA. E-mail: lwang1@med.miami.edu

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  • Karen Nuytemans,

    1. John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida
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  • Guney Bademci,

    1. John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida
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  • Cherylyn Jauregui,

    1. John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida
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  • Eden R. Martin,

    1. John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida
    2. Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida
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  • William K. Scott,

    1. John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida
    2. Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida
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  • Jeffery M. Vance,

    1. John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida
    2. Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida
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  • Stephan Zuchner

    1. John P. Hussman Institute for Human Genomics, University of Miami, Miller School of Medicine, Miami, Florida
    2. Dr. John T. Macdonald Foundation Department of Human Genetics, University of Miami, Miller School of Medicine, Miami, Florida
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  • Contract grant sponsors: NIH NINDS (2P50NS071674-02); James and Esther King/ Biomedical Research Program (1KN 14).

  • Communicated by Christine Van Broeckhoven

ABSTRACT

A high density comparative genomic hybridization array was designed to evaluate CNVs in the genomic region of six familial PD genes in 181 PD cases and 67 controls. No CNV was found in PARK7, ATP13A2, PINK1, and LRRK2. Intronic-only CNVs were found in SNCA and PARK2 but were not associated with PD risk. A whole-gene duplication of SNCA was found in one case. The allele frequency of PARK2 exonic CNV is significantly higher in cases than in controls (P = 0.02), higher in early-onset (AAO ≤ 40) than in late-onset cases (P = 0.001), and higher in familial than in sporadic cases (P = 0.005). Except for single exon 2 duplications, all PARK2 exonic CNVs have different breakpoints, even when the same exon(s) were involved. In conclusion, except for SNCA and PARK2, CNVs are not a major contributing mechanism for the familial PD genes examined. The majority of PARK2 exonic CNVs are not recurrent.

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