title: Comprehensive analysis of gene expression in human retina and supporting tissues.
abstract: Understanding the influence of gene expression on the molecular mechanisms underpinning human phenotypic diversity is fundamental to being able to predict health outcomes and treat disease. We have carried out whole transcriptome expression analysis on a series of eight normal human postmortem eyes by RNA sequencing. Here we present data showing that ∼80% of the transcriptome is expressed in the posterior layers of the eye and that there is significant differential expression not only between the layers of the posterior part of the eye but also between locations of a tissue layer. These differences in expression also extend to alternative splicing and splicing factors. Differentially expressed genes are enriched for genes associated with psychiatric, immune and cardiovascular disorders. Enrichment categories for gene ontology included ion transport, synaptic transmission and visual and sensory perception. Lastly, allele-specific expression was found to be significant for CFH, C3 and CFB, which are known risk genes for age-related macular degeneration. These expression differences should be useful in determining the underlying biology of associations with common diseases of the human retina, retinal pigment epithelium and choroid and in guiding the analysis of the genomic regions involved in the control of normal gene expression.
authors.affiliation: Department of Biostatistics and Epidemiology.
authors.forename: Mingyao
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Biostatistics and Epidemiology.
authors.forename: Cheng
authors.initials: C
authors.lastname: Jia
authors.affiliation: Department of Ophthalmology.
authors.forename: Krista L
authors.initials: KL
authors.lastname: Kazmierkiewicz
authors.affiliation: Department of Ophthalmology.
authors.forename: Anita S
authors.initials: AS
authors.lastname: Bowman
authors.affiliation: Center for Applied Genomics.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Biostatistics and Epidemiology.
authors.forename: Yichuan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: College of Medicine, Drexel University, Philadelphia, PA 19104, USA.
authors.forename: Neel A
authors.initials: NA
authors.lastname: Gupta
authors.affiliation: Department of Ophthalmology.
authors.forename: Harini V
authors.initials: HV
authors.lastname: Gudiseva
authors.affiliation: Department of Ophthalmology.
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: Yee
authors.affiliation: Department of Ophthalmology.
authors.forename: Mijin
authors.initials: M
authors.lastname: Kim
authors.affiliation: Department of Dermatology and.
authors.forename: Tzvete
authors.initials: T
authors.lastname: Dentchev
authors.affiliation: Retina Specialists of Alabama, Birmingham, AL 35294, USA Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, AL 35294, USA.
authors.forename: James A
authors.initials: JA
authors.lastname: Kimble
authors.affiliation: Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, AL 35294, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Parker
authors.affiliation: Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, AL 35294, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Messinger
authors.affiliation: Department of Pediatrics, The Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA Division of Pulmonary Medicine and The Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA 19104, USA.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: Department of Ophthalmology, University of Alabama School of Medicine, Birmingham, AL 35294, USA.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Curcio
authors.affiliation: Department of Ophthalmology stamboli@mail.med.upenn.edu.
authors.forename: Dwight
authors.initials: D
authors.lastname: Stambolian
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001344:Autopsy; D002829:Choroid / Q000378:metabolism*; D003176:Complement C3 / Q000235:genetics; D011415:Complement Factor B / Q000235:genetics; D017242:Complement Factor H / Q000235:genetics; D005136:Eye Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D008268:Macular Degeneration / Q000175:diagnosis / Q000235:genetics; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D055213:Retinal Pigment Epithelium / Q000378:metabolism*; D012307:Risk Factors; D059467:Transcriptome
chemical_list: D003176:Complement C3; D005136:Eye Proteins; D017242:Complement Factor H; D011415:Complement Factor B