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Abstract #46419 Published in IGR 13-3
Copy Number Variations (CNVs) and Primary Open Angle Glaucoma (POAG)
Davis L; Meyer K; Schindler E; Beck J; Rudd D; Grundstad AJ; Scheetz T; Braun T; Fingert J; Kwon WAInvestigative Ophthalmology and Visual Science 2011;
See also comment(s) by Michael Hauser •
PURPOSE: 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). Here we present data 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 copy number variation using a combination of 500K Affymetrix SNP GeneChip Microarrays and 5.0 Affymetrix SNP GeneChip Microarrays. The signal intensity data generated from these arrays was then analyzed with multiple CNV detection programs including CNAG v2.0, PennCNV, and dChip. RESULTS: A total of 11 validated CNVs have been identified as recurrent in the POAG set and absent from the age matched controls. This set includes CNVs on chromosome 5q23.1 (DMXL1, DTWD2), 20p12 (PAK7), 12q14 (C12orf56, XPOT, TBK1, 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 supports the role of these CNV implicated genes in vision related processes. Additionally, CNV locations of DMXL1 and PAK7 overlap previously identified linkage signals for glaucoma on chromosomes 5p23.1 and 20p12, respectively (Sud et al., 2008; Pang et al., 2006). CONCLUSIONS: Here we present data consistent with the hypothesis that rare copy number variation plays a role in the development of POAG.
Department of Psychiatry, University of Illinois, Chicago, IL; USA.
Classification:
3.4.1 Linkage studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)
