Multi-omics analysis in human retina uncovers ultraconserved cis-regulatory elements at rare eye disease loci.
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All Authors
Lopez Soriano, V.
Duenas Rey, A.
Mukherjee, R.
Coppieters, F.
Bauwens, M.
Willaert, A.
De Baere, E.
LTHT Author
Mukherjee, Rajarshi
LTHT Department
Ophthalmology
Non Medic
Publication Date
2024
Item Type
Journal Article
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Subject Headings
Abstract
Cross-species genome comparisons have revealed a substantial number of ultraconserved non-coding elements (UCNEs). Several of these elements have proved to be essential tissue- and cell type-specific cis-regulators of developmental gene expression. Here, we characterize a set of UCNEs as candidate CREs (cCREs) during retinal development and evaluate the contribution of their genomic variation to rare eye diseases, for which pathogenic non-coding variants are emerging. Integration of bulk and single-cell retinal multi-omics data reveals 594 genes under potential cis-regulatory control of UCNEs, of which 45 are implicated in rare eye disease. Mining of candidate cis-regulatory UCNEs in WGS data derived from the rare eye disease cohort of Genomics England reveals 178 ultrarare variants within 84 UCNEs associated with 29 disease genes. Overall, we provide a comprehensive annotation of ultraconserved non-coding regions acting as cCREs during retinal development which can be targets of non-coding variation underlying rare eye diseases.
Journal
Nature communications