Genetic analyses of human fetal retinal pigment epithelium gene expression suggest ocular disease mechanisms
| Autor: | Ming Chen, Stephen B. Montgomery, Nathan S. Abell, Xin Li, Gillie Benchorin, Douglas Vollrath, Dean Bok, Jane Hu, Brunilda Balliu, Boxiang Liu, Melissa A. Calton, Michael J. Gloudemans |
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| Rok vydání: | 2018 |
| Předmět: |
Candidate gene
genetic structures Quantitative Trait Loci Medicine (miscellaneous) Gene Expression Genome-wide association study Retinal Pigment Epithelium Biology Quantitative trait locus General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences 0302 clinical medicine Fetus Risk Factors medicine Myopia Humans Allele lcsh:QH301-705.5 Cells Cultured 030304 developmental biology Genetics 0303 health sciences Retinal pigment epithelium Macular degeneration Chromosome Mapping Genetic Variation medicine.disease eye diseases Nonsense Mediated mRNA Decay Computational biology and bioinformatics Alcohol Oxidoreductases medicine.anatomical_structure lcsh:Biology (General) Eye disorder sense organs General Agricultural and Biological Sciences Energy Metabolism Transcriptome Functional genomics 030217 neurology & neurosurgery Genome-Wide Association Study |
| Zdroj: | Communications Biology Communications Biology, Vol 2, Iss 1, Pp 1-13 (2019) |
| ISSN: | 2399-3642 |
| Popis: | The retinal pigment epithelium (RPE) serves vital roles in ocular development and retinal homeostasis but has limited representation in large-scale functional genomics datasets. Understanding how common human genetic variants affect RPE gene expression could elucidate the sources of phenotypic variability in selected monogenic ocular diseases and pinpoint causal genes at genome-wide association study (GWAS) loci. We interrogated the genetics of gene expression of cultured human fetal RPE (fRPE) cells under two metabolic conditions and discovered hundreds of shared or condition-specific expression or splice quantitative trait loci (e/sQTLs). Co-localizations of fRPE e/sQTLs with age-related macular degeneration (AMD) and myopia GWAS data suggest new candidate genes, and mechanisms by which a common RDH5 allele contributes to both increased AMD risk and decreased myopia risk. Our study highlights the unique transcriptomic characteristics of fRPE and provides a resource to connect e/sQTLs in a critical ocular cell type to monogenic and complex eye disorders. Boxiang Liu, Melissa Calton et al. report expression and splice quantitative trait locus analyses for human fetal retinal epithelium (fRPE) cells under two metabolic conditions. They identify loci linked to inherited ocular diseases and new candidate genes for age-related macular degeneration and myopia. |
| Databáze: | OpenAIRE |
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