Variation in MUTYH expression in Arabian horses with Cerebellar Abiotrophy.
Abstract: Cerebellar Abiotrophy (CA) is a neurodegenerative disease in Arabian horses affecting the cerebellum, more specifically the Purkinje neurons. Although CA occurs in several domestic species, CA in Arabian horses is unique in that a single nucleotide polymorphism (SNP) has been associated with the disease. Total RNA sequencing (RNA-seq) was performed on CA-affected horses to address the molecular mechanism underlying the disease. This research expands upon the RNA-seq work by measuring the impact of the CA-associated SNP on the candidate gene MutY homolog (MUTYH) and its regulation, isoform-specific expression and protein localization. We hypothesized that the CA-associated SNP compromises the promoter region of MUTYH, leading to differential expression of its isoforms. Our research demonstrates that the CA-associated SNP introduces a new binding site for a novel transcription factor (Myelin Transcription Factor-1 Like protein, MYT1L). In addition, CA-affected horses show differential expression of a specific isoform of MUTYH as well as different localization in the Purkinje and granular neurons of the cerebellum.
Copyright © 2017 Elsevier B.V. All rights reserved.
Publication Date: 2017-11-02 PubMed ID: 29103988PubMed Central: PMC5905334DOI: 10.1016/j.brainres.2017.10.034Google Scholar: Lookup
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Summary
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This research paper explores the mechanisms of Cerebellar Abiotrophy (CA) in Arabian horses, particularly focusing on a single nucleotide polymorphism (SNP) associated with the disease. The study examines the effect of this SNP on MUTYH gene regulation, its isoform-specific expression, and protein localization.
Understanding Cerebellar Abiotrophy
- The paper discusses Cerebellar Abiotrophy (CA), a neurodegenerative disorder prevalent in Arabian horses that affects the Purkinje neurons in the cerebellum.
- While the disease occurs in different domestic species, the focus of this study is on Arabian horses due to a specific single nucleotide polymorphism (SNP) that has been identified as being associated with the disease in this breed.
RNA-Sequencing and the Role of MUTYH
- Total RNA sequencing (RNA-seq) was conducted on horses affected by CA as a means of investigating the molecular mechanisms behind the disease.
- The paper builds on this work by studying the influence of the CA-related SNP on the candidate gene MutY homolog (MUTYH). The study not only investigated the gene’s regulation, but also the isoform-specific expression and protein localization.
The Hypothesis and Findings
- The central hypothesis of the research is that the CA-associated SNP compromises the promoter region of MUTYH, leading to the differential expression of its isoforms.
- The study found that the CA-associated SNP does indeed introduce a new binding site for a novel transcription factor dubbed the Myelin Transcription Factor-1 Like protein (MYT1L).
- The researchers also observed differential expression of a specific isoform of MUTYH in CA-affected horses, along with varying localization in the cerebellum’s Purkinje and granular neurons.
Implications of the Study
- This study provides valuable insights into the molecular mechanisms of CA in Arabian horses and could potentially guide future research and treatment strategies.
- The differential expression and localization of MUTYH observed in this study suggest a possible target for therapeutic intervention.
- The identification of MYT1L as a novel transcription factor suggests a potential pathway by which the CA-associated SNP could be influencing gene regulation, thereby affecting the progress of the disease.
Cite This Article
APA
Scott EY, Woolard KD, Finno CJ, Penedo MCT, Murray JD.
(2017).
Variation in MUTYH expression in Arabian horses with Cerebellar Abiotrophy.
Brain Res, 1678, 330-336.
https://doi.org/10.1016/j.brainres.2017.10.034 Publication
Researcher Affiliations
- University of California, Davis, Department of Animal Science, USA.
- University of California, Davis, Department of Pathology, Microbiology & Immunology, USA.
- University of California, Davis, Department of Population Health and Reproduction, USA.
- University of California, Davis, Veterinary Genetics Laboratory, USA.
- University of California, Davis, Department of Animal Science, USA; University of California, Davis, Department of Population Health and Reproduction, USA. Electronic address: jdmurray@ucdavis.edu.
MeSH Terms
- Animals
- Cerebellar Diseases / genetics
- Cerebellar Diseases / pathology
- Cerebellar Diseases / veterinary
- Cerebellum / pathology
- DNA Glycosylases / genetics
- DNA Mutational Analysis
- Heredodegenerative Disorders, Nervous System / genetics
- Heredodegenerative Disorders, Nervous System / veterinary
- Horses / genetics
- Polymorphism, Single Nucleotide / genetics
- Purkinje Cells / metabolism
- Purkinje Cells / pathology
Grant Funding
- K01 OD015134 / NIH HHS
- L40 TR001136 / NCATS NIH HHS
Conflict of Interest Statement
Competing interests. Authors declare no competing interest.
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