On the molecular genetics of retinal dystrophies and glaucoma

Abstract

The central aim of this thesis was the elucidation of the underlying molecular pathologies of inherited diseases of the eye. Previous linkage studies on a large Spanish kindred (family FA-84), segregating adRP, resulted in the localisation of an adRP gene (RPIO) to chromosome 7q31.3 (Jordan et al., 1993). Linkage and haplotype data were re-evaluated in this family and two novel genes were adopted as candidates. These genes encoded a metabotropic glutamate receptor, GRM8, and a diacylglycerol kinase, DGK1. Prior to mutation screening it was necessary to determine much o f the structure of GRM8. The gene was screened using both single-stranded conformational polym orphism (SSCP) analysis and direct sequencing. A small portion o f the gene for which the intron/exon structure was unknown was screened following RT-PCR on illegitimate transcripts in blood. No mutations were identified in GRM8. SSCP analysis o f the DGK1 gene resulted in the identification of a two-allele polymorphism which also allowed exclusion o f this gene as RP10.