Investigation Of Candidate Loci For Primary Open Angle Glaucoma In A Brazilian Family Through SNP Array

Abstract

Purpose: : Glaucoma is one of the major causes of irreversible blindness worldwide, characterized by progressive loss of optic nerve ganglion cells, associated with correspondent visual field damage. Among several forms of glaucoma, the most prevalent is the primary open angle glaucoma (POAG). The increase of intraocular pressure is the most important risk factor for the development of POAG. There are at least 14 loci (GLC1A - GLC1N) associated with POAG identified from genetic mapping studies, most of them involving families that follow a Mendelian inheritance pattern but only three genes were identified. The first described gene was myocilin (MYOC - GLC1A), followed by optineurin (OPTN or Optic Neuropathy Induced Protein - GLC1E) and WD Repeat-Containing Protein 36 (WDR36 - GLC1G) genes. The purpose of this study was to evaluate regions in the genome associated with glaucoma through linkage study in one POAG informative family, by means of single nucleotide polymorphism (SNP) microarray.

Methods: : Comprehensive ophthalmic evaluation was performed and genomic DNA obtained from one Brazilian family (11 individuals) with POAG. Genome-wide linkage analysis was conducted using the Affymetrix 10K SNP array and analyzed by JINGLEFIX and MERLIN softwares.

Results: : The SNP array generated 6067 valid SNPs. One chromosomal region (2p22-23) with lod scores varying from 2.04 to 2.40 was obtained.

Conclusions: : Although the results do not show values of lod scores above 3.00, this region contains potential candidate genes for POAG.

Keywords: genetics • gene mapping • optic nerve