title: Copy number variations and primary open-angle glaucoma.
abstract: OBJECTIVE
  This study sought to investigate the role of rare copy number variation (CNV) in age-related disorders of blindness, with a focus on primary open-angle glaucoma (POAG). Data are reported from a whole-genome copy number screen in a large cohort of 400 individuals with POAG and 500 age-matched glaucoma-free subjects.
  
  
  METHODS
  DNA samples from patients and controls were tested for CNVs using a combination of two microarray platforms. The signal intensity data generated from these arrays were then analyzed with multiple CNV detection programs including CNAG version 2.0, PennCNV, and dChip.
  
  
  RESULTS
  A total of 11 validated CNVs were identified as recurrent in the POAG set and absent in the age-matched control set. This set included CNVs on 5q23.1 (DMXL1, DTWD2), 20p12 (PAK7), 12q14 (C12orf56, XPOT, TBK1, and RASSF3), 12p13.33 (TULP3), and 10q34.21 (PAX2), among others. The CNVs presented here are exceedingly rare and are not found in the Database of Genomic Variants. Moreover, expression data from ocular tissue support the role of these CNV-implicated genes in vision-related processes. In addition, CNV locations of DMXL1 and PAK7 overlap previously identified linkage signals for glaucoma on 5p23.1 and 20p12, respectively.
  
  
  CONCLUSIONS
  The data are consistent with the hypothesis that rare CNV plays a role in the development of POAG.
authors.affiliation: Department of Psychiatry, University of Illinois, Chicago, Illinois, USA.
authors.forename: Lea K
authors.initials: LK
authors.lastname: Davis
authors.forename: Kacie J
authors.initials: KJ
authors.lastname: Meyer
authors.forename: Emily I
authors.initials: EI
authors.lastname: Schindler
authors.forename: John S
authors.initials: JS
authors.lastname: Beck
authors.forename: Danielle S
authors.initials: DS
authors.lastname: Rudd
authors.forename: A Jason
authors.initials: AJ
authors.lastname: Grundstad
authors.forename: Todd E
authors.initials: TE
authors.lastname: Scheetz
authors.forename: Terry A
authors.initials: TA
authors.lastname: Braun
authors.forename: John H
authors.initials: JH
authors.lastname: Fingert
authors.forename: Wallace L M
authors.initials: WL
authors.lastname: Alward
authors.forename: Young H
authors.initials: YH
authors.lastname: Kwon
authors.forename: James C
authors.initials: JC
authors.lastname: Folk
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Russell
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Wassink
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.forename: Edwin M
authors.initials: EM
authors.lastname: Stone
mesh_terms: D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations / Q000235:genetics*; D005260:Female; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study; D005902:Glaucoma, Open-Angle / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction