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Rgcs1, a dominant QTL that affects retinal ganglion cell death after optic nerve crush in mice

DOI: 10.1186/1471-2202-9-74

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Abstract:

Genome wide mapping of the F2 mice using microsatellite markers, detected a single highly significant quantitative trait locus in a 25 cM (58 Mb) interval on chromosome 5 (Chr5.loc34-59 cM). No interacting loci were detected at the resolution of this screen. We have designated this locus as Retinal ganglion cell susceptible 1, Rgcs1. In silico analysis of this region revealed the presence of 578 genes or expressed sequence tags, 4 of which are highly expressed in the ganglion cell layer of the mammalian retina, and 2 of which are suspected susceptibility alleles in chronic neurodegenerative diseases. In addition, 25 genes contain 36 known single nucleotide polymorphisms that create nonsynonymous amino acid changes between the two parental strains. Collectively, this analysis has identified 7 potential candidate genes that may affect ganglion cell death.The process of ganglion cell death is likely one of the many facets of glaucoma susceptibility. A novel dominant locus has been identified that affects sensitivity of ganglion cells to optic nerve crush. The allele responsible for this sensitivity may also be a susceptibility allele for glaucoma.Glaucoma is a blinding disease characterized by the progressive death of retinal ganglion cells. The principal risk factor for glaucoma is elevated intraocular pressure (IOP) [1-3]. Biomechanical engineering studies suggest that IOP-related stress is focused on ganglion cell axons exiting the eye through the lamina cribrosa [4,5]. Current models suggest that optic nerve glia are adversely affected and that this leads first to destruction of the ganglion cell axon, and secondarily, to the apoptotic death of the ganglion cell soma (reviewed by [6,7]).Glaucoma is a complex genetic disease [8]. After elevated IOP, family history is the next most important risk factor [9,10]. While many important studies have revealed a great deal about the genetics of this disease, the majority of these have been restricted to relatively rare form

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