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Mapping the cis -regulatory architecture of the human retina reveals noncoding genetic variation in disease.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2020 Apr 21; Vol. 117 (16), pp. 9001-9012. Date of Electronic Publication: 2020 Apr 07. - Publication Year :
- 2020
-
Abstract
- The interplay of transcription factors and cis -regulatory elements (CREs) orchestrates the dynamic and diverse genetic programs that assemble the human central nervous system (CNS) during development and maintain its function throughout life. Genetic variation within CREs plays a central role in phenotypic variation in complex traits including the risk of developing disease. We took advantage of the retina, a well-characterized region of the CNS known to be affected by pathogenic variants in CREs, to establish a roadmap for characterizing regulatory variation in the human CNS. This comprehensive analysis of tissue-specific regulatory elements, transcription factor binding, and gene expression programs in three regions of the human visual system (retina, macula, and retinal pigment epithelium/choroid) reveals features of regulatory element evolution that shape tissue-specific gene expression programs and defines regulatory elements with the potential to contribute to Mendelian and complex disorders of human vision.<br />Competing Interests: The authors declare no competing interest.
- Subjects :
- Adult
Animals
DNA Mutational Analysis
Epigenomics
Female
Genetic Variation
Humans
Male
Mice
Middle Aged
Mutation
RNA-Seq
Retina growth & development
Retinal Diseases pathology
Species Specificity
Evolution, Molecular
Gene Expression Regulation, Developmental
Regulatory Sequences, Nucleic Acid genetics
Retina pathology
Retinal Diseases genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 117
- Issue :
- 16
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 32265282
- Full Text :
- https://doi.org/10.1073/pnas.1922501117