Copy Number Variation Analysis of a Primary Open Angle Glaucoma Brazilian Familiy

Abstract

Purpose: : Glaucoma is one of the major causes of irreversible blindness worldwide due to progressive loss of optic nerve ganglion cells. Fourteen loci (GLC1A - GLC1N) have been associated with primary open-angle glaucoma (POAG). Copy number variations or CNVs play a major role in genetic variation but have recently been related to both simple and complex human genetic diseases. The purpose of this study was to evaluate a Brazilian family with POAG and determine the difference in CNVs between affected and non-affected individuals.

Methods: : Comprehensive ophthalmic evaluation was conducted and genomic DNA obtained from five patients and five controls from the same family. The CNV pattern was determined using the Affymetrix Genome-Wide Human SNP Array 6.0 and data were analyzed by Genotyping Console and Partek softwares. Comparisons were made from Cases X Controls, Cases X HapMap and Controls X HapMap.

Results: : A total of 534 CNVs were identified when comparing cases and controls from the same family, being amplifications more frequent in cases than in controls when large CNVs (> 100Kb) are evaluated. When small CNVs (< 100Kb) are analyzed, deletions are more frequent in cases than in controls. The average number of CNVs per individual was 246.0 versus 190.6 from the analysis through the Genotyping Console. Imbalances between cases and controls were observed in regions 8p23.1, 4q32.2, 1p34.3, 3q29, 7q35, 7q11.21 e 5q13.2, some of them confirmed by both softwares.

Conclusions: : This is the first report of CNV evaluation in the Brazilian population, using patients and controls from the same family to reduce the interference of genetic background. The validation is necessary to confirm the existence of such CNVs, however, these data give the first clue to a larger investigation including one CNV which is located at previously GLC1F locus associated to POAG (7q35).

Keywords: genetics • optic nerve • gene microarray