Transcriptome diversity and differential expression in supporting limb laminitis.
Abstract: Laminitis results in impaired tissue integrity and Inflammation of the epidermal and dermal lamellae connecting the hoof capsule to the underlying distal phalanx and causes loss-of-use, poor quality of life and euthanasia in horses. Historically, studies to better understand the etiology of laminitis by documenting changes in gene expression were hampered by the paucity of gene annotation specific to hoof tissues. Next-generation sequencing enables improvements to annotation by incorporating equine- and hoof-specific transcripts. Here we characterize the hoof lamellar tissue transcriptome of naturally occurring supporting limb laminitis (SLL) using archived lamellar tissue from Thoroughbred racehorses consisting of 13 SLL hospital cases and seven age-matched control horses. This was achieved using: 1) Applied transcriptome annotation by long-read sequencing to document transcript diversity and 2) short-read RNA sequencing to document changes in gene expression correlating to the developmental and acute stages of naturally occurring SLL. 1.99Gbp of long-read transcriptome sequencing deeply documented 5067 unique loci, while short read RNA-seq under very stringent quality filters described 66 differentially expressed loci. Functional analysis of these loci revealed alterations in cell replication and growth, stress response and leukocyte recruitment and activation pathways. Differential expression of the Ezrin and TIMP3 genes suggests they may have utility as biomarkers for laminitis disease, while NR1D1 and genes relevant to the inflammasome are promising targets for novel pharmacological treatments.
Copyright © 2021 Elsevier B.V. All rights reserved.
Publication Date: 2021-11-09 PubMed ID: 34839133DOI: 10.1016/j.vetimm.2021.110353Google Scholar: Lookup
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- Journal Article
Summary
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This research investigates the genetic changes that occur in horses with supporting limb laminitis (SLL), a painful hoof condition, using cutting-edge sequencing technology. It unveils differences in gene expression which could help identify new treatments and biomarkers for the disease.
Research Background
- The study focuses on supporting limb laminitis (SLL), a chronic inflammation of the hoof tissue in horses leading to discomfort, immobility, and potentially euthanasia.
- Past research aiming to understand laminitis was obstructed due to limited genomic information related to hoof tissue.
- The advent of next-generation sequencing has enhanced the ability to study specific genes in hoof tissue.
Methodology
- The research team obtained lamellar tissue (the layer connecting the hoof with the underlying bone) from 13 Thoroughbred horses with SLL and seven control horses without SLL.
- They used long-read sequencing to uncover a comprehensive range of gene transcripts in the sample.
- They then used short-read RNA sequencing to pinpoint specific changes in gene expression linked to the onset and progression of SLL.
Findings
- In the long-read sequencing, they identified 1.99Gbp sequences covering 5067 unique locations on the genome, demonstrating the vast transcript diversity.
- The short-read RNA sequence under stringent quality controls identified 66 distinct locations where gene expression was different in the SLL samples versus the control group.
- Functional analysis revealed that these changes were connected to cellular replication, stress response, and leukocyte (white blood cells) recruitment and activation pathways.
- Two genes, Ezrin and TIMP3, showed significant variation in expression, suggesting they might serve as useful biomarkers for detecting and monitoring SLL.
- Additionally, NR1D1 and other genes related to the inflammasome (a part of the immune response) could provide new targets for pharmacological treatment of SLL.
Implications
- The study provides new insights into the genetic changes involved in SLL and lays the groundwork for the development of novel diagnostic and therapeutic approaches for this debilitating condition in horses.
Cite This Article
APA
Holl HM, Armstrong C, Galantino-Homer H, Brooks SA.
(2021).
Transcriptome diversity and differential expression in supporting limb laminitis.
Vet Immunol Immunopathol, 243, 110353.
https://doi.org/10.1016/j.vetimm.2021.110353 Publication
Researcher Affiliations
- Department of Animal Sciences, UF Genetics Institute, University of Florida, Gainesville, FL, United States.
- Department of Clinical Studies/New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United States.
- Department of Clinical Studies/New Bolton Center, School of Veterinary Medicine, University of Pennsylvania, Kennett Square, PA, United States.
- Department of Animal Sciences, UF Genetics Institute, University of Florida, Gainesville, FL, United States. Electronic address: Samantha.brooks@ufl.edu.
MeSH Terms
- Animals
- Foot Diseases / genetics
- Foot Diseases / veterinary
- Hoof and Claw / pathology
- Horse Diseases / genetics
- Horses
- Inflammation / genetics
- Inflammation / veterinary
- Lameness, Animal / genetics
- Quality of Life
- Transcriptome
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