Mapping the -regulatory architecture of the human retina reveals noncoding genetic variation in disease.

TitleMapping the -regulatory architecture of the human retina reveals noncoding genetic variation in disease.
Publication TypeJournal Article
Year of Publication2020
AuthorsCherry, TJ, Yang, MG, Harmin, DA, Tao, P, Timms, AE, Bauwens, M, Allikmets, R, Jones, EM, Chen, R, De Baere, E, Greenberg, ME
JournalProc Natl Acad Sci U S A
Date Published2020 Apr 21
KeywordsAdult, Animals, DNA Mutational Analysis, Epigenomics, Evolution, Molecular, Female, Gene Expression Regulation, Developmental, Genetic Variation, Humans, Male, Mice, Middle Aged, Mutation, Regulatory Sequences, Nucleic Acid, Retina, Retinal Diseases, RNA-Seq, Species Specificity

The interplay of transcription factors and -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.

Alternate JournalProc Natl Acad Sci U S A
PubMed ID32265282
PubMed Central IDPMC7183164
Grant ListP30 EY019007 / EY / NEI NIH HHS / United States
R01 EY029315 / EY / NEI NIH HHS / United States
R37 NS028829 / NS / NINDS NIH HHS / United States

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