title: High-resolution arrays reveal burden of copy number variations on Parkinson disease genes associated with increased disease risk in random cohorts.
abstract: BACKGROUND
  Parkinson disease (PD) is a neurological disease responsible for a considerable rate of mortality and morbidity in the society. Since the symptoms of the disease appear much later than the actual onset of neuron degeneration, a majority of cases remain undiagnosed until the manifestation of the symptoms.
  
  
  OBJECTIVE
  In order to investigate the existence of such susceptibility in the population, we analyzed Copy Number Variation (CNV) influences on PD genes in 1715 individuals from 12 different populations.
  
  
  RESULTS
  Overall, 16 CNV-PD genes, 3 known to be causal and 13 associated, were found to be significantly enriched. PARK2, was under heavy burden with ~1% of the population containing CNV in the exonic region. The impact of these genes on the genome and disease pathway was analyzed using several genome analysis tools. Protein interaction network of CNV-PD genes revealed a complex interaction of molecules forming a major hub by the α-Synuclein, whose direct interactors, LRRK2, PARK2 and ATP13A2 are under CNV influence.
  
  
  CONCLUSIONS
  We hypothesize that CNVs may not be the initiating event in the pathogenesis of PD and remain latent until additional secondary hits are acquired and also propose novel genes that may fall under the PD pathway which contribute in pathogenesis.
authors.affiliation: a Genetics and Genomics Lab, Department of Genetics and Genomics , University of Mysore , Mysore , India.
authors.forename: Megha N
authors.initials: MN
authors.lastname: Murthy
authors.affiliation: a Genetics and Genomics Lab, Department of Genetics and Genomics , University of Mysore , Mysore , India.
authors.forename: Avinash M
authors.initials: AM
authors.lastname: Veerappa
authors.affiliation: b Department of Neurology , JSS Hospital , Mysore , India.
authors.forename: Keshava B
authors.initials: KB
authors.lastname: Seshachalam
authors.affiliation: a Genetics and Genomics Lab, Department of Genetics and Genomics , University of Mysore , Mysore , India.
authors.forename: Nallur B
authors.initials: NB
authors.lastname: Ramachandra
mesh_terms: D000465:Algorithms; D015331:Cohort Studies; D056915:DNA Copy Number Variations / Q000235:genetics*; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / Q000235:genetics; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010300:Parkinson Disease / Q000208:ethnology* / Q000235:genetics*; D010641:Phenotype; D006180:Proton-Translocating ATPases / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: C514983:ATP13A2 protein, human; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D006180:Proton-Translocating ATPases
keywords: Affymetrix Genome-Wide Human SNP Array 6.0; Copy Number Variations (CNV); Ingenuity Pathway Analysis; PD Network and pathway; Parkinson Disease (PD); Structural variation