title: Identification of rod- and cone-specific expression signatures to identify candidate genes for retinal disease.
abstract: Recent advances in technology have greatly increased our ability to identify genetic variants in individuals with retinal disease. However, determining which are likely to be pathogenic remains a challenging task. Using a transgenic coneless (cl) mouse model, together with rodless (rd/rd) and rodless/coneless (rd/rd cl) mice, we have characterised patterns of gene expression in the rod and cone photoreceptors at a genome-wide level. We examined the expression of >27,000 genes in the mice lacking rods, cones or both and compared them with wild type animals. We identified a list of 418 genes with highly significant changes in expression in one or more of the transgenic strains. Pathway analysis confirmed that expected Gene Ontology terms such as phototransduction were over-represented amongst these genes. However, many of these genes have no previously known function in the retina. Gene set enrichment analysis further demonstrated that the mouse orthologues of known human retinal disease genes were significantly enriched amongst those genes with decreased expression. Comparison of our data to human disease loci with no known causal genetic changes has highlighted genes with significant changes in expression making these strong candidates for further screening. These data add to the current literature through the utilisation of the specific cl and rd/rd cl models. Moreover, this study identifies genes that appear to be implicated in photoreceptor function thereby providing a valuable filter for variants identified by high-throughput sequencing in individuals with retinal disease.
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Levels 5 and 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Richard
authors.initials: R
authors.lastname: Holt
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Levels 5 and 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Laurence
authors.initials: L
authors.lastname: Brown
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Levels 5 and 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Broadgate
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Levels 5 and 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Butler
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Levels 5 and 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Aarti
authors.initials: A
authors.lastname: Jagannath
authors.affiliation: Oxford Eye Hospital, Level LG1 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Susan
authors.initials: S
authors.lastname: Downes
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Levels 5 and 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK.
authors.forename: Stuart
authors.initials: S
authors.lastname: Peirson
authors.affiliation: Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neurosciences, University of Oxford, Levels 5 and 6 West Wing, John Radcliffe Hospital, Headley Way, Oxford OX3 9DU, UK. Electronic address: stephanie.halford@eye.ox.ac.uk.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Halford
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D051379:Mice; D008822:Mice, Transgenic; D017949:Retinal Cone Photoreceptor Cells / Q000378:metabolism*; D012164:Retinal Diseases / Q000235:genetics*; D017948:Retinal Rod Photoreceptor Cells / Q000378:metabolism*
keywords: Cones; Disease; Expression; Mouse models; Photoreceptors; Retina; Rods; Vision