Genome-wide Linkage Scan for Primary Angle Closure Glaucoma

Abstract

Abstract: : Purpose: Primary angle closure glaucoma (PACG) is a major cause of glaucoma in Asia. Racial differences in the prevalence of PACG and the familial tendency towards the disease suggest a genetic basis for the condition. After excluding linkage to loci for genes associated with short axial length and previously reported glaucoma loci, a genome-wide linkage scan was undertaken on a large Singaporean PACG pedigree to identify genetic loci for the condition. Methods: After detailed clinical evaluation, genomic DNA samples were obtained from 15 family members (8 affected). Linkage analysis was performed with 400 polymorphic microsatellite markers spaced at 10 cM intervals spanning the genome. Two-point linkage analysis was performed by the MLINK program of the FASTLINK version 4.0P package. Results: The pedigree demonstrated autosomal dominant inheritance. Affected individuals had a mean anterior chamber depth of 2.6 + 0.2 mm (range: 2.3 to 3.1 mm) and mean axial length of 22.3 + 0.8 mm (range: 19.9 to 23.5 mm). Two point lod scores of >1.00 was detected in 8 different chromosomal locations in the pedigree (chromosomes 1q, 3p, 7p, 10p, 10q, 11q, 13q, 18p) with the highest LOD score being obtained on chromosome 10q (LOD>3 at θ=.00). Further work is in progress to confirm this result. Conclusions: Based on a genome-wide linkage scan, a first locus for PACG has been identified on chromosome 10q. This analysis is intended to determine the genetic basis of PACG.

Keywords: genetics • anterior chamber