ArticlePLoS genetics2015
Functional assessment of disease-associated regulatory variants in vivo using a versatile dual colour transgenesis strategy in zebrafish.
Article in PLoS genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 23 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- Mechanisms underlying disease-causing variants in promoters and enhancers.Nature genetics · 2026Review
- The orofacial cleft risk gene IRF6 is a target gene of SOX9 in cranial neural crest cells.Journal of molecular medicine (Berlin, Germany) · 2026Article
- Article
- Rapid and quantitative functional interrogation of human enhancer variant activity in live mice.Nature communications · 2025Article
- Short-read whole genome sequencing identifies causative variants in most individuals with previously unexplained aniridia.Journal of medical genetics · 2024Article
- Rapid and Quantitative Functional Interrogation of Human Enhancer Variant Activity in Live Mice.bioRxiv : the preprint server for biology · 2023Article
- Zebrafish regulatory genomic resources for disease modelling and regeneration.Disease models & mechanisms · 2023Article
- Facial analytics based on a coordinate extrapolation system (zFACE) for morphometric phenotyping of developing zebrafish.Disease models & mechanisms · 2023Article
- Review
- Quantitative spatial and temporal assessment of regulatory element activity in zebrafish.eLife · 2021Article
- Article
- Perspective of the GEMSTONE Consortium on Current and Future Approaches to Functional Validation for Skeletal Genetic Disease Using Cellular, Molecular and Animal-Modeling Techniques.Frontiers in endocrinology · 2021Review
- Quantitative Dissection of the ProximalFrontiers in cell and developmental biology · 2021Article
- Lampreys, the jawless vertebrates, contain three Pax6 genes with distinct expression in eye, brain and pancreas.Scientific reports · 2019Article
- Zebrafish: A Powerful Model for Understanding the Functional Relevance of Noncoding Region Mutations in Human Genetic Diseases.Biomedicines · 2019Review
- Genome sequencing-the dawn of a game-changing era.Heredity · 2019Review
- Pattern of fin rays along the antero-posterior axis based on their connection to distal radials.Zoological letters · 2019Article
- SBE6: a novel long-range enhancer involved in driving sonic hedgehog expression in neural progenitor cells.Open biology · 2016Article
- Article
- Association of TFAP2A gene polymorphism with susceptibility to non-syndromic cleft lip with or without palate risk in south Indian population.Meta gene · 2016Article
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 7 institutions in 2 countries.
Funding
Abstract
Disruption of gene regulation by sequence variation in non-coding regions of the genome is now recognised as a significant cause of human disease and disease susceptibility. Sequence variants in cis-regulatory elements (CREs), the primary determinants of spatio-temporal gene regulation, can alter transcription factor binding sites. While technological advances have led to easy identification of disease-associated CRE variants, robust methods for discerning functional CRE variants from background variation are lacking. Here we describe an efficient dual-colour reporter transgenesis approach in zebrafish, simultaneously allowing detailed in vivo comparison of spatio-temporal differences in regulatory activity between putative CRE variants and assessment of altered transcription factor binding potential of the variant. We validate the method on known disease-associated elements regulating SHH, PAX6 and IRF6 and subsequently characterise novel, ultra-long-range SOX9 enhancers implicated in the craniofacial abnormality Pierre Robin Sequence. The method provides a highly cost-effective, fast and robust approach for simultaneously unravelling in a single assay whether, where and when in embryonic development a disease-associated CRE-variant is affecting its regulatory function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.