The broad objective of this proposal is to identify a disease gene responsible for Stargardt's macular dystrophy (STGD) and to elucidate the underlying molecular mechanism of macular degeneration. It is important to study the genetic basis of STGD, as this disease is the most common juvenile macular degeneration. Furthermore, STGD shares important clinical and histopathological features with age-related macular degeneration (AMD), and certain mutations in a gene of recessive STGD have been reported to be associated with a fraction of AMD. These observations make STGD3 a unique genetic model for AMD. Therefore, understand the molecular mechanism of STGD3 should lead to novel insights into the pathogenesis of macular degeneration. Elucidation of the function of the STGD3 gene may increase our understanding of retinal cell biology in general. Finally, this study may provide information for pursuing novel strategies for treatment of macular degeneration. In this proposed research, a positional cloning approach will be used to identify the STGD3 gene. Fir the minimal genetic interval for STGD3 locus will be refined by genetic linkage study using new pedigrees and new polymorphic markers. Second, search for mutations in the candidate genes and Expressed Sequence Tags (ESTs) in pedigrees linked to STGD3 will be conducted. Third, a YAC contig spanning the minimal genetic interval will be constructed and cloning of expressed cDNA sequences will be performed by cDNA selection and Exon-trapping.
| Yang, Zhenglin; Lin, Wei; Moshfeghi, Darius M et al. (2003) A novel mutation in the RDS/Peripherin gene causes adult-onset foveomacular dystrophy. Am J Ophthalmol 135:213-8 |
