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Multi-omics analysis in human retina uncovers ultraconserved cis-regulatory elements at rare eye disease loci

Author

Listed:
  • Victor Lopez Soriano

    (Ghent University
    Center for Medical Genetics, Ghent University Hospital)

  • Alfredo Dueñas Rey

    (Ghent University
    Center for Medical Genetics, Ghent University Hospital)

  • Rajarshi Mukherjee

    (St James’s University Hospital)

  • Frauke Coppieters

    (Ghent University
    Center for Medical Genetics, Ghent University Hospital
    Ghent University)

  • Miriam Bauwens

    (Ghent University
    Center for Medical Genetics, Ghent University Hospital)

  • Andy Willaert

    (Ghent University
    Center for Medical Genetics, Ghent University Hospital)

  • Elfride De Baere

    (Ghent University
    Center for Medical Genetics, Ghent University Hospital)

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.

Suggested Citation

  • Victor Lopez Soriano & Alfredo Dueñas Rey & Rajarshi Mukherjee & Frauke Coppieters & Miriam Bauwens & Andy Willaert & Elfride De Baere, 2024. "Multi-omics analysis in human retina uncovers ultraconserved cis-regulatory elements at rare eye disease loci," Nature Communications, Nature, vol. 15(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45381-1
    DOI: 10.1038/s41467-024-45381-1
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    References listed on IDEAS

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