title: Genome-wide analysis of copy number variations identifies PARK2 as a candidate gene for autism spectrum disorder.
abstract: BACKGROUND
  Autism spectrum disorder (ASD) is an early-onset neurodevelopmental disorder with complex genetic underpinning in its etiology. Copy number variations (CNVs) as one of the genetic factors associated with ASD have been addressed in recent genome-wide association studies (GWAS). However, the significance of CNV has not been well investigated in non-Caucasian ASD population.
  
  
  METHODS
  To identify the pathogenic CNVs responsible for ASD in Han Chinese, we performed a segment-based GWAS of CNV in 335 ASD cases and 1093 healthy controls using Affymetrix single nucleotide polymorphism (SNP) array by focusing on case-specific CNVs. PARK2 was one of the important genes with several case-specific regions overlapped on it. The findings were validated in the initial screen sample set and replicated in another sample set by real-time quantitative PCR (qPCR).
  
  
  RESULTS
  A total of six CNVs at 6q26 that spanned different exons of PARK2 were identified. The PARK2 expression level was down-regulated at exon-dependent manner in cases with either deletion or duplication. The result revealed that the gene function might be disrupted by exonic deletion and duplication. We also observed that the ASD case with exonic duplication demonstrated a more severe interference of PARK2 expression and the clinical feature than the ones with deletion at the exons 2-4 of the PARK2 gene.
  
  
  CONCLUSIONS
  Our finding provides evidence to support that CNVs affecting PARK2 function might contribute to genetic etiology of a proportion of cases with ASD. The intriguing results of this work warrant further study on characterizing the functional impact of various exonic CNVs on the PARK2 gene.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT00494754.
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, 10002 Taiwan.|Graduate Institute of Brain Sciences, National Yang-Ming University, Taipei, 11221 Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Yin
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, 10002 Taiwan.
authors.forename: Hsin-I
authors.initials: HI
authors.lastname: Chen
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529 Taiwan.
authors.forename: Ling-Hui
authors.initials: LH
authors.lastname: Li
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, 10002 Taiwan.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Chien
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, 10002 Taiwan.|Section on Molecular Neurobiology, National Institute of Mental Health, National Institutes of Health, Bethesda, 20892 USA.
authors.forename: Hsiao-Mei
authors.initials: HM
authors.lastname: Liao
authors.affiliation: Department of Child Psychiatry, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, 83301 Taiwan.
authors.forename: Miao Chun
authors.initials: MC
authors.lastname: Chou
authors.affiliation: Department of Child Psychiatry, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, 83301 Taiwan.
authors.forename: Wen-Jiun
authors.initials: WJ
authors.lastname: Chou
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, 10002 Taiwan.
authors.forename: Wen-Che
authors.initials: WC
authors.lastname: Tsai
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, 10002 Taiwan.
authors.forename: Yen-Nan
authors.initials: YN
authors.lastname: Chiu
authors.affiliation: Department of Child Psychiatry, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, 33302 Taiwan.
authors.forename: Yu-Yu
authors.initials: YY
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529 Taiwan.
authors.forename: Chen-Zen
authors.initials: CZ
authors.lastname: Lo
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529 Taiwan.
authors.forename: Jer-Yuarn
authors.initials: JY
authors.lastname: Wu
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529 Taiwan.
authors.forename: Yuan-Tsong
authors.initials: YT
authors.lastname: Chen
authors.affiliation: Department of Psychiatry, National Taiwan University Hospital and College of Medicine, No. 7, Chung-Shan South Road, Taipei, 10002 Taiwan.
authors.forename: Susan Shur-Fen
authors.initials: SS
authors.lastname: Gau
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000235:genetics; D000067877:Autism Spectrum Disorder / Q000209:etiology / Q000235:genetics*; D002648:Child; D002681:China; D015331:Cohort Studies; D056915:DNA Copy Number Variations; D015536:Down-Regulation; D005091:Exons; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D016017:Odds Ratio; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D044767:Ubiquitin-Protein Ligases; C111567:parkin protein
keywords: Autism spectrum disorder (ASD); Copy number variations (CNVs); Family study; Gene expression; PARK2