Copy number variations and primary open-angle glaucoma

Lea K Davis; Kacie J Meyer; Emily I Schindler; John S Beck; Danielle S Rudd; A Jason Grundstad; Todd E Scheetz; Terry A Braun; John H Fingert; Wallace L M Alward; Young H Kwon; James C Folk; Stephen R Russell; Thomas H Wassink; Val C Sheffield; Edwin M Stone

doi:10.1167/iovs.10-5606

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Copy number variations and primary open-angle glaucoma

Journal article

Open access

Peer reviewed

Copy number variations and primary open-angle glaucoma

Lea K Davis, Kacie J Meyer, Emily I Schindler, John S Beck, Danielle S Rudd, A Jason Grundstad, Todd E Scheetz, Terry A Braun, John H Fingert, Wallace L M Alward, …

Investigative ophthalmology & visual science, Vol.52(10), pp.7122-7133

2011

DOI: 10.1167/iovs.10-5606

PMCID: PMC3207715

PMID: 21310917

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Abstract

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. 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. 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. The data are consistent with the hypothesis that rare CNV plays a role in the development of POAG.

Genome-Wide Association Study

Oligonucleotide Array Sequence Analysis

Glaucoma, Open-Angle - genetics

Humans

Middle Aged

Glaucoma, Open-Angle - diagnosis

Male

DNA Copy Number Variations - genetics

Reverse Transcriptase Polymerase Chain Reaction

Genome, Human - genetics

Comparative Genomic Hybridization

Polymorphism, Single Nucleotide - genetics

Female

Details

Title: Subtitle: Copy number variations and primary open-angle glaucoma
Creators: Lea K Davis - Department of Psychiatry, University of Illinois, Chicago, Illinois, USA
Kacie J Meyer
Emily I Schindler
John S Beck
Danielle S Rudd
A Jason Grundstad
Todd E Scheetz
Terry A Braun
John H Fingert
Wallace L M Alward
Young H Kwon
James C Folk
Stephen R Russell
Thomas H Wassink
Val C Sheffield
Edwin M Stone
Resource Type: Journal article
Publication Details: Investigative ophthalmology & visual science, Vol.52(10), pp.7122-7133
DOI: 10.1167/iovs.10-5606
PMID: 21310917
PMCID: PMC3207715
NLM abbreviation: Invest Ophthalmol Vis Sci
ISSN: 0146-0404
eISSN: 1552-5783
Publisher: United States
Grant note: T32 GM008629 / NIGMS NIH HHS R01 EY016822 / NEI NIH HHS R01-EY-010564 / NEI NIH HHS R01 EY018825 / NEI NIH HHS R01-EY-016822 / NEI NIH HHS R01 EY016822-06 / NEI NIH HHS R01 EY016822-07 / NEI NIH HHS T32GM008629 / NIGMS NIH HHS R01 EY016822-08 / NEI NIH HHS R01 EY010564 / NEI NIH HHS
Language: English
Date published: 2011
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Electrical and Computer Engineering; Molecular Physiology and Biophysics; Psychiatry; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
Record Identifier: 9983979984002771

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