IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-45381-1.html
   My bibliography  Save this article

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
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-45381-1
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-45381-1?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Jesse R. Dixon & Siddarth Selvaraj & Feng Yue & Audrey Kim & Yan Li & Yin Shen & Ming Hu & Jun S. Liu & Bing Ren, 2012. "Topological domains in mammalian genomes identified by analysis of chromatin interactions," Nature, Nature, vol. 485(7398), pages 376-380, May.
    2. Helena Santos-Rosa & Robert Schneider & Andrew J. Bannister & Julia Sherriff & Bradley E. Bernstein & N. C. Tolga Emre & Stuart L. Schreiber & Jane Mellor & Tony Kouzarides, 2002. "Active genes are tri-methylated at K4 of histone H3," Nature, Nature, vol. 419(6905), pages 407-411, September.
    3. Dimitrios Vitsios & Ryan S. Dhindsa & Lawrence Middleton & Ayal B. Gussow & Slavé Petrovski, 2021. "Prioritizing non-coding regions based on human genomic constraint and sequence context with deep learning," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    4. Alvaro Rada-Iglesias & Ruchi Bajpai & Tomek Swigut & Samantha A. Brugmann & Ryan A. Flynn & Joanna Wysocka, 2011. "A unique chromatin signature uncovers early developmental enhancers in humans," Nature, Nature, vol. 470(7333), pages 279-283, February.
    5. Len A. Pennacchio & Nadav Ahituv & Alan M. Moses & Shyam Prabhakar & Marcelo A. Nobrega & Malak Shoukry & Simon Minovitsky & Inna Dubchak & Amy Holt & Keith D. Lewis & Ingrid Plajzer-Frick & Jennifer , 2006. "In vivo enhancer analysis of human conserved non-coding sequences," Nature, Nature, vol. 444(7118), pages 499-502, November.
    6. Noah Dukler & Mehreen R. Mughal & Ritika Ramani & Yi-Fei Huang & Adam Siepel, 2022. "Extreme purifying selection against point mutations in the human genome," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Jin Woo Oh & Michael A. Beer, 2024. "Gapped-kmer sequence modeling robustly identifies regulatory vocabularies and distal enhancers conserved between evolutionarily distant mammals," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    2. Marko Dunjić & Felix Jonas & Gilad Yaakov & Roye More & Yoav Mayshar & Yoach Rais & Ayelet-Hashahar Orenbuch & Saifeng Cheng & Naama Barkai & Yonatan Stelzer, 2023. "Histone exchange sensors reveal variant specific dynamics in mouse embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    3. Dongmei Wang & Haimin Li & Navdeep S. Chandel & Yali Dou & Rui Yi, 2023. "MOF-mediated histone H4 Lysine 16 acetylation governs mitochondrial and ciliary functions by controlling gene promoters," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    4. Iksoo Huh & Isabel Mendizabal & Taesung Park & Soojin V Yi, 2018. "Functional conservation of sequence determinants at rapidly evolving regulatory regions across mammals," PLOS Computational Biology, Public Library of Science, vol. 14(10), pages 1-21, October.
    5. Chaitali Chakraborty & Itzel Nissen & Craig A. Vincent & Anna-Carin Hägglund & Andreas Hörnblad & Silvia Remeseiro, 2023. "Rewiring of the promoter-enhancer interactome and regulatory landscape in glioblastoma orchestrates gene expression underlying neurogliomal synaptic communication," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    6. Marta Losa & Iros Barozzi & Marco Osterwalder & Viviana Hermosilla-Aguayo & Angela Morabito & Brandon H. Chacón & Peyman Zarrineh & Ausra Girdziusaite & Jean Denis Benazet & Jianjian Zhu & Susan Macke, 2023. "A spatio-temporally constrained gene regulatory network directed by PBX1/2 acquires limb patterning specificity via HAND2," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    7. Zhen-Hui Wang & Xin-Feng Wang & Tianyuan Lu & Ming-Rui Li & Peng Jiang & Jing Zhao & Si-Tong Liu & Xue-Qi Fu & Jonathan F. Wendel & Yves Peer & Bao Liu & Lin-Feng Li, 2022. "Reshuffling of the ancestral core-eudicot genome shaped chromatin topology and epigenetic modification in Panax," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    8. Matthias Wielscher & Pooja R. Mandaviya & Brigitte Kuehnel & Roby Joehanes & Rima Mustafa & Oliver Robinson & Yan Zhang & Barbara Bodinier & Esther Walton & Pashupati P. Mishra & Pascal Schlosser & Ro, 2022. "DNA methylation signature of chronic low-grade inflammation and its role in cardio-respiratory diseases," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    9. Bhuwan Khatri & Kandice L. Tessneer & Astrid Rasmussen & Farhang Aghakhanian & Tove Ragna Reksten & Adam Adler & Ilias Alevizos & Juan-Manuel Anaya & Lara A. Aqrawi & Eva Baecklund & Johan G. Brun & S, 2022. "Genome-wide association study identifies Sjögren’s risk loci with functional implications in immune and glandular cells," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    10. Chong Wang & Xiang Liu & Jun Liang & Yohei Narita & Weiyue Ding & Difei Li & Luyao Zhang & Hongbo Wang & Merrin Man Long Leong & Isabella Hou & Catherine Gerdt & Chang Jiang & Qian Zhong & Zhonghui Ta, 2023. "A DNA tumor virus globally reprograms host 3D genome architecture to achieve immortal growth," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Liyuan Zhou & Qiongzi Qiu & Qing Zhou & Jianwei Li & Mengqian Yu & Kezhen Li & Lingling Xu & Xiaohui Ke & Haiming Xu & Bingjian Lu & Hui Wang & Weiguo Lu & Pengyuan Liu & Yan Lu, 2022. "Long-read sequencing unveils high-resolution HPV integration and its oncogenic progression in cervical cancer," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    12. Vinícius G. Contessoto & Olga Dudchenko & Erez Lieberman Aiden & Peter G. Wolynes & José N. Onuchic & Michele Pierro, 2023. "Interphase chromosomes of the Aedes aegypti mosquito are liquid crystalline and can sense mechanical cues," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    13. Yi Li & James Lee & Lu Bai, 2024. "DNA methylation-based high-resolution mapping of long-distance chromosomal interactions in nucleosome-depleted regions," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    14. Hossein Salari & Geneviève Fourel & Daniel Jost, 2024. "Transcription regulates the spatio-temporal dynamics of genes through micro-compartmentalization," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    15. Alon Diament & Tamir Tuller, 2015. "Improving 3D Genome Reconstructions Using Orthologous and Functional Constraints," PLOS Computational Biology, Public Library of Science, vol. 11(5), pages 1-22, May.
    16. Andrea Wilderman & Eva D’haene & Machteld Baetens & Tara N. Yankee & Emma Wentworth Winchester & Nicole Glidden & Ellen Roets & Jo Dorpe & Sandra Janssens & Danny E. Miller & Miranda Galey & Kari M. B, 2024. "A distant global control region is essential for normal expression of anterior HOXA genes during mouse and human craniofacial development," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    17. Buki Kwon & Mervin M. Fansler & Neil D. Patel & Jihye Lee & Weirui Ma & Christine Mayr, 2022. "Enhancers regulate 3′ end processing activity to control expression of alternative 3′UTR isoforms," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    18. Lindsay Lee & Hongyu Yu & Bojing Blair Jia & Adam Jussila & Chenxu Zhu & Jiawen Chen & Liangqi Xie & Antonina Hafner & Shreya Mishra & Duan Dennis Wang & Caterina Strambio-De-Castillia & Alistair Boet, 2023. "SnapFISH: a computational pipeline to identify chromatin loops from multiplexed DNA FISH data," Nature Communications, Nature, vol. 14(1), pages 1-7, December.
    19. Sonali Narang & Yohana Ghebrechristos & Nikki A. Evensen & Nina Murrell & Sylwia Jasinski & Talia H. Ostrow & David T. Teachey & Elizabeth A. Raetz & Timothee Lionnet & Matthew Witkowski & Iannis Aifa, 2024. "Clonal evolution of the 3D chromatin landscape in patients with relapsed pediatric B-cell acute lymphoblastic leukemia," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    20. Da Lin & Weize Xu & Ping Hong & Chengchao Wu & Zhihui Zhang & Siheng Zhang & Lingyu Xing & Bing Yang & Wei Zhou & Qin Xiao & Jinyue Wang & Cong Wang & Yu He & Xi Chen & Xiaojian Cao & Jiangwei Man & A, 2022. "Decoding the spatial chromatin organization and dynamic epigenetic landscapes of macrophage cells during differentiation and immune activation," Nature Communications, Nature, vol. 13(1), pages 1-19, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45381-1. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.