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Home / Equine Research Bank / Cerebellum / Defining Trends in Global Gene Expression in Arabian Horses ...
Cerebellum (London, England)2016; 16(2); 462-472; doi: 10.1007/s12311-016-0823-8

Defining Trends in Global Gene Expression in Arabian Horses with Cerebellar Abiotrophy.

Abstract: Equine cerebellar abiotrophy (CA) is a hereditary neurodegenerative disease that affects the Purkinje neurons of the cerebellum and causes ataxia in Arabian foals. Signs of CA are typically first recognized either at birth to any time up to 6 months of age. CA is inherited as an autosomal recessive trait and is associated with a single nucleotide polymorphism (SNP) on equine chromosome 2 (13074277G>A), located in the fourth exon of TOE1 and in proximity to MUTYH on the antisense strand. We hypothesize that unraveling the functional consequences of the CA SNP using RNA-seq will elucidate the molecular pathways underlying the CA phenotype. RNA-seq (100 bp PE strand-specific) was performed in cerebellar tissue from four CA-affected and five age-matched unaffected horses. Three pipelines for differential gene expression (DE) analysis were used (Tophat2/Cuffdiff2, Kallisto/EdgeR, and Kallisto/Sleuth) with 151 significant DE genes identified by all three pipelines in CA-affected horses. TOE1 (Log2(foldchange) = 0.92, p = 0.66) and MUTYH (Log2(foldchange) = 1.13, p = 0.66) were not differentially expressed. Among the major pathways that were differentially expressed, genes associated with calcium homeostasis and specifically expressed in Purkinje neurons, CALB1 (Log2(foldchange) = -1.7, p < 0.01) and CA8 (Log2(foldchange) = -0.97, p < 0.01), were significantly down-regulated, confirming loss of Purkinje neurons. There was also a significant up-regulation of markers for microglial phagocytosis, TYROBP (Log2(foldchange) = 1.99, p < 0.01) and TREM2 (Log2(foldchange) = 2.02, p < 0.01). These findings reaffirm a loss of Purkinje neurons in CA-affected horses along with a potential secondary loss of granular neurons and activation of microglial cells.
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Publication Date: 2016-10-07 PubMed ID: 27709457PubMed Central: PMC5336519DOI: 10.1007/s12311-016-0823-8Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This study focuses on understanding the genetic cause of cerebellar abiotrophy (CA), a degenerative neurological disease in Arabian horses, by examining genes on chromosome 2 and their functions using RNA-seq technology.

Overview of Cerebellar Abiotrophy

  • Equine cerebellar abiotrophy (CA) is a genetic disease that primarily affects Arabian horses. This hereditary disorder leads to the degeneration of a type of neuron called the Purkinje neurons located in the cerebellum, causing a lack of coordinated movements (ataxia) in foals. The symptoms are usually identifiable at birth or within six months.
  • CA is an autosomal recessive disease, meaning both parents must carry a copy of the mutated gene to pass it on to their offspring. Previous studies have linked CA to a mutation (single nucleotide polymorphism, SNP), on the horse’s second chromosome.

Aim of the Research and Methodology

  • The goal of the research was to investigate the genetic basis of CA with a focus on the functional consequences of the identified SNP using RNA sequencing (RNA-seq).
  • The researchers performed RNA-seq on cerebellar tissue samples from four horses affected by CA and five unaffected horses. Three separate data analysis pipelines were utilized to identify differential gene expression.

Key Findings

  • 151 genes were identified with significantly different expression levels in the CA-affected horses across all three data analysis pipelines.
  • The researchers found that the genes TOE1 and MUTYH associated with the SNP were not differentially expressed.
  • Significant downregulation was found in CALB1 and CA8, both genes associated with calcium homeostasis and specifically expressed in Purkinje neurons. This supports the observation of Purkinje neuron loss in CA.
  • Markers for microglial phagocytosis (a function of the brain’s immune cells), TYROBP and TREM2, were significantly upregulated, suggesting increased activation of microglial cells and potentially a secondary loss of other neuron types.

Implications

  • The outcomes of this research provide more detailed insight into the molecular pathways involved in CA. While the mutation-associated genes TOE1 and MUTYH were not differentially expressed, the data revealed other genes and biological processes critical to the disease.
  • The differential expression of genes related to Purkinje neurons’ function and the activation of microglial cells suggest a complex pathology for CA that involves not only a loss of specific neuron types but also other processes such as immune response.

Cite This Article

APA
Scott EY, Penedo MCT, Murray JD, Finno CJ. (2016). Defining Trends in Global Gene Expression in Arabian Horses with Cerebellar Abiotrophy. Cerebellum, 16(2), 462-472. https://doi.org/10.1007/s12311-016-0823-8

Publication

Cerebellum (London, England)
ISSN: 1473-4230
NlmUniqueID: 101089443
Country: United States
Language: English
Volume: 16
Issue: 2
Pages: 462-472

Researcher Affiliations

Scott, E Y
  • Department of Animal Science, University of California, Davis, USA.
Penedo, M C T
  • Veterinary Genetics Laboratory, School of Veterinary Medicine, University of California, Davis, USA.
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, USA.
Murray, J D
  • Department of Animal Science, University of California, Davis, USA. JDMurray@ucdavis.edu.
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, USA. JDMurray@ucdavis.edu.
Finno, C J
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California, Davis, USA. cjfinno@ucdavis.edu.

MeSH Terms

  • Animals
  • Cerebellum / growth & development
  • Cerebellum / metabolism
  • Cluster Analysis
  • DNA Glycosylases / genetics
  • DNA Glycosylases / metabolism
  • Female
  • Gene Expression
  • Heredodegenerative Disorders, Nervous System / genetics
  • Heredodegenerative Disorders, Nervous System / metabolism
  • Heredodegenerative Disorders, Nervous System / veterinary
  • Horse Diseases / genetics
  • Horse Diseases / metabolism
  • Horses
  • Male
  • Polymerase Chain Reaction
  • Polymorphism, Single Nucleotide
  • Transcriptome
  • Unsupervised Machine Learning

Grant Funding

  • K01 OD015134 / NIH HHS
  • L40 TR001136 / NCATS NIH HHS

Conflict of Interest Statement

Conflict of Interest. The authors declare that they have no conflict of interest.

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Citations

This article has been cited 5 times.
  1. Giron C, Hélie P, Parent J, Boutin M, St-Jean G. Clinical, imaging and histopathological characterization of a series of three cats with cerebellar cortical degeneration. BMC Vet Res 2024 Jun 19;20(1):263.
    doi: 10.1186/s12917-024-04127-3pubmed: 38890680google scholar: lookup
  2. Scott EY, Woolard KD, Finno CJ, Murray JD. Cerebellar Abiotrophy Across Domestic Species. Cerebellum 2018 Jun;17(3):372-379.
    doi: 10.1007/s12311-017-0914-1pubmed: 29294214google scholar: lookup
  3. Aleman M, Finno CJ, Weich K, Penedo MCT. Investigation of Known Genetic Mutations of Arabian Horses in Egyptian Arabian Foals with Juvenile Idiopathic Epilepsy. J Vet Intern Med 2018 Jan;32(1):465-468.
    doi: 10.1111/jvim.14873pubmed: 29171123google scholar: lookup
  4. Scott EY, Woolard KD, Finno CJ, Penedo MCT, Murray JD. Variation in MUTYH expression in Arabian horses with Cerebellar Abiotrophy. Brain Res 2018 Jan 1;1678:330-336.
    doi: 10.1016/j.brainres.2017.10.034pubmed: 29103988google scholar: lookup
  5. Mansour TA, Scott EY, Finno CJ, Bellone RR, Mienaltowski MJ, Penedo MC, Ross PJ, Valberg SJ, Murray JD, Brown CT. Tissue resolved, gene structure refined equine transcriptome. BMC Genomics 2017 Jan 20;18(1):103.
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