Previously Identified Genetic Variants in ADGRL3 Are not Associated with Risk for Equine Degenerative Myeloencephalopathy across Breeds.
Abstract: Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurologic disease that has been reported in young horses from a wide range of breeds. The disease is inherited and associated with vitamin E deficiency during the first two years of life, resulting in bilateral symmetric ataxia. A missense mutation (chr3:71,917,591 C > T) within adhesion G protein-coupled receptor L3 (ADGRL3) was recently associated with risk for EDM in the Caspian breed. In order to confirm these findings, genotyping of this missense mutation, along with the three other associated single nucleotide polymorphisms (SNPs) in the genomic region, was carried out on 31 postmortem-confirmed eNAD/EDM cases and 43 clinically phenotyped controls from various breeds. No significant association was found between eNAD/EDM confirmed cases and genotype at any of the four identified SNPs (P > 0.05), including the nonsynonymous variant (EquCab2.0 chr3:71,917,591; allelic P = 0.85). These findings suggest that the four SNPs, including the missense variant in the ADGRL3 region, are not associated with risk for eNAD/EDM across multiple breeds of horses.
Publication Date: 2019-09-05 PubMed ID: 31491999PubMed Central: PMC6770705DOI: 10.3390/genes10090681Google Scholar: Lookup
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- Journal Article
- Research Support
- N.I.H.
- Extramural
- Research Support
- Non-U.S. Gov't
Summary
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This research article investigates the possible genetic causes of a neurological disease in horses known as equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM). It focuses on one genetic variant previously linked to the disease in one horse breed, but finds no strong association across multiple horse breeds.
Background
- Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurological disorder affecting horses. It is associated with a vitamin E deficiency in young horses and leads to bilateral symmetric ataxia, a loss of muscle coordination and balance.
- In previous research, a specific missense genetic mutation within the adhesion G protein-coupled receptor L3 (ADGRL3) was linked as a potential risk factor for EDM in the Caspian breed of horses.
- A missense mutation is a type of genetic mutation that results in a different amino acid being added to a protein, potentially altering its function.
Study Purpose and Method
- The goal of this research was to ascertain if the previously identified mutation in ADGRL3 and three other single nucleotide polymorphisms (SNPs) are indeed associated with eNAD/EDM not only in Caspian horses, but in various other horse breeds as well. SNP’s are variations at a single position in a DNA sequence among individuals.
- To do this, genotyping, or identifying the genetic information of an individual by their DNA sequence, was carried out on 31 horses that had been post-mortem confirmed to have eNAD/EDM and 43 healthy control horses from various breeds.
Findings
- The researchers found no significant association between the four SNPs (including the missense mutation in the ADGRL3 gene) and confirmed cases of eNAD/EDM across the different horse breeds that were studied.
- In statistical terms, the chance that this observation occurred by mere luck and not due to a true association was high (p > 0.05).
Conclusion
- The results suggest that the four genetic variants studied, including the missense mutation in the ADGRL3 gene, are not linked to an increased risk for eNAD/EDM when considering a variety of horse breeds.
- This means that the genetic basis for eNAD/EDM across various horse breeds is still not well understood and requires more research.
Cite This Article
APA
Marquardt SA, Wilcox CV, Burns EN, Peterson JA, Finno CJ.
(2019).
Previously Identified Genetic Variants in ADGRL3 Are not Associated with Risk for Equine Degenerative Myeloencephalopathy across Breeds.
Genes (Basel), 10(9).
https://doi.org/10.3390/genes10090681 Publication
Researcher Affiliations
- Department of Population, Health and Reproduction at the University of California, Davis, Davis, CA 95616, USA. samarquardt@ucdavis.edu.
- Department of Population, Health and Reproduction at the University of California, Davis, Davis, CA 95616, USA. cvwilcox@ucdavis.edu.
- Department of Population, Health and Reproduction at the University of California, Davis, Davis, CA 95616, USA. enburns@ucdavis.edu.
- Department of Population, Health and Reproduction at the University of California, Davis, Davis, CA 95616, USA. janel.peterson@bcm.edu.
- Department of Population, Health and Reproduction at the University of California, Davis, Davis, CA 95616, USA. cjfinno@ucdavis.edu.
MeSH Terms
- Animals
- Horse Diseases / genetics
- Horses / genetics
- Mutation, Missense
- Neuroaxonal Dystrophies / genetics
- Neuroaxonal Dystrophies / veterinary
- Polymorphism, Single Nucleotide
- Receptors, G-Protein-Coupled / genetics
- Receptors, Peptide / genetics
Grant Funding
- L40 TR001136 / NCATS NIH HHS
Conflict of Interest Statement
The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
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