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

Timothy J. Cherry, Marty G. Yang, David A. Harmin, Peter Tao, Andrew E. Timms, Miriam Bauwens, Rando Allikmets, Evan M. Jones, Rui Chen, Elfride De Baere, Michael E. Greenberg
2020 Proceedings of the National Academy of Sciences of the United States of America  
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
more » ... s, 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.
doi:10.1073/pnas.1922501117 pmid:32265282 fatcat:cly2lgnfwvfoxhzywxkc72oiwy