Purchase this article with an account.
Colin E. Willoughby, Judith Lechner, Jia Wei, Edward W. Dervan, Durga P. Dash, Joanne Logan, Simon J. Rankin, Colm J. O'Brien; Allelotyping In Primary Open-angle Glaucoma Using Snp Microarrays And DNA Pooling. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2418.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
Genome-wide association studies (GWAS) using SNP arrays are a fundamental approach to identify genes associated with complex genetic disorders like POAG. One way to address the cost, time and labour that are involved in large-scale genotyping is to carry out analyses not on individual DNA samples, but pools made up of DNA from many individuals: allelotyping or SNP Microarrays and DNA Pooling (SNP-MaP). This approach was applied to detect alleles associated with high and low tension glaucoma.
Caucasian patients with high tension (HTG) and normal tension (NTG) POAG were recruited following careful phenotyping from the Departments of Ophthalmology in Belfast and Dublin. Extracted DNA was accurately quantified and pools were constructed using equimolar amounts of DNA from each patient or control. Pooled DNA was allelotyped on the Affymetrix SNP 6.0 Array. Pooled array data was analysed using GPFrontend and GPGraphics software tools and the GenePool algorithm to rank SNPs and assess SNP clustering.
Four DNA pools consisting of 98 HTG patients in two separate pools (55 Belfast and 43 Dublin cases), 90 NTG patients and 90 Caucasian population controls were analysed on the Affymetrix SNP 6.0 Array. A number of chromosomal loci harbouring clusters of high ranking SNPs in biologically plausible candidate genes have been identified which require replication in further pools and SNP genotyping of individual samples. In particular, initial analysis of SNPs in the mtDNA has identified four significant target regions in NTG and one in HTG cases not seen in controls.
Preliminary data suggests that allelotyping using SNP-MaP is a cost effective strategy to identify genes associated with POAG. The role of the mitochondrial genome in POAG requires further exploration.
This PDF is available to Subscribers Only