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Home / Equine Research Bank / J Vet Intern Med / Pedigree analysis and exclusion of alpha-tocopherol transfer...
Journal of veterinary internal medicine2012; 27(1); 177-185; doi: 10.1111/jvim.12015

Pedigree analysis and exclusion of alpha-tocopherol transfer protein (TTPA) as a candidate gene for neuroaxonal dystrophy in the American Quarter Horse.

Abstract: Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM) is a neurodegenerative disorder affecting young horses of various breeds that resembles ataxia with vitamin E deficiency in humans, an inherited disorder caused by mutations in the alpha-tocopherol transfer protein gene (TTPA). To evaluate variants found upon sequencing TTPA in the horse, the mode of inheritance for NAD/EDM had to be established. Objective: NAD/EDM in the American Quarter Horse (QH) is caused by a mutation in TTPA. Methods: 88 clinically phenotyped (35 affected [ataxia score ≥2], 53 unaffected) QHs with a diagnosis of NAD/EDM with 6 affected and 4 unaffected cases confirmed at postmortem examination. Methods: Pedigrees and genotypes across 54,000 single nucleotide polymorphism (SNP) markers were assessed to determine heritability and mode of inheritance of NAD/EDM. TTPA sequence of exon/intron boundaries was evaluated in 2 affected and 2 control horses. An association analysis was performed by 71 SNPs surrounding TTPA and 8 SNPs within TTPA that were discovered by sequencing. RT-PCR for TTPA was performed on mRNA from the liver of 4 affected and 4 control horses. Results: Equine NAD/EDM appears to be inherited as a polygenic trait and, within this family of QHs, demonstrates high heritability. Sequencing of TTPA identified 12 variants. No significant association was found using the 79 available variants in and surrounding TTPA. RT-PCR yielded PCR products of equivalent sizes between affected cases and controls. Conclusions: NAD/EDM demonstrates heritability in this family of QHs. Variants in TTPA are not responsible for NAD/EDM in this study population.
Copyright © 2012 by the American College of Veterinary Internal Medicine.
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Publication Date: 2012-11-27 PubMed ID: 23186252PubMed Central: PMC4557866DOI: 10.1111/jvim.12015Google Scholar: Lookup
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  • Journal Article
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  • Extramural
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  • U.S. Gov't
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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.

The research explores the genetic basis of a neurodegenerative disorder in American Quarter Horses known as equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM). The study finds that this disorder has high heritability and is polygenic in nature, but it is not linked to mutations in the alpha-tocopheral transfer protein gene (TTPA), which is associated with a similar condition in humans.

Objective of the Research

  • The main objective of this research study was to determine if a mutation in the alpha-tocopherol transfer protein gene (or TTPA gene for short) is responsible for causing neuroaxonal dystrophy/equine degenerative myeloencephalopathy (NAD/EDM), a neurodegenerative disorder in the American Quarter Horse breed.

Methods Used in the Research

  • For this study, the researchers took a sample of 88 American Quarter Horses that had been clinically phenotyped or evaluated to determine their phenotype. This sample included 35 horses that were affected by NAD/EDM and 53 horses that were not.
  • Additionally, the researchers performed a post-mortem examination on six affected and four unaffected cases.
  • The pedigrees and genotypes of the horses were assessed using 54,000 single nucleotide polymorphism (SNP) markers in order to establish the mode of inheritance and heritability of NAD/EDM.
  • The researchers also sequenced the TTPA gene in two affected and two control horses and performed an association analysis using the identified variants in and surrounding TTPA.
  • Finally, they conducted RT-PCR for TTPA on mRNA extracted from the liver of four affected and four control horses.

Results of the Research

  • Through pedigree analysis, the researchers concluded that the equine NAD/EDM trait is inherited as a polygenic trait, meaning that it is controlled by multiple genes.
  • The study found high heritability of NAD/EDM within the family of American Quarter Horses tested, indicating that the trait is largely determined by genetics.
  • The sequencing of the TTPA gene identified 12 variants. However, the researchers found no significant association between these variants and NAD/EDM.
  • The RT-PCR test did not show any significant differences in the sizes of PCR products between affected cases and controls.

Conclusions from the Research

  • The research concluded that while NAD/EDM has high heritability and is a polygenic trait in American Quarter Horses, it does not seem to be associated with variations in the TTPA gene.
  • This is a significant finding because TTPA mutations cause a disorder in humans that’s similar to NAD/EDM. These results suggest that the genetic causes of NAD/EDM in horses may be different than the causes of similar diseases in humans.

Cite This Article

APA
Finno CJ, Famula T, Aleman M, Higgins RJ, Madigan JE, Bannasch DL. (2012). Pedigree analysis and exclusion of alpha-tocopherol transfer protein (TTPA) as a candidate gene for neuroaxonal dystrophy in the American Quarter Horse. J Vet Intern Med, 27(1), 177-185. https://doi.org/10.1111/jvim.12015

Publication

Journal of veterinary internal medicine
ISSN: 1939-1676
NlmUniqueID: 8708660
Country: United States
Language: English
Volume: 27
Issue: 1
Pages: 177-185

Researcher Affiliations

Finno, C J
  • Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA, USA. finn0100@umn.edu
Famula, T
    Aleman, M
      Higgins, R J
        Madigan, J E
          Bannasch, D L

            MeSH Terms

            • Animals
            • Carrier Proteins / genetics
            • Female
            • Genetic Predisposition to Disease
            • Horse Diseases / genetics
            • Horses
            • Male
            • Neuroaxonal Dystrophies / genetics
            • Neuroaxonal Dystrophies / veterinary
            • Pedigree

            Grant Funding

            • K01 OD015134 / NIH HHS
            • T32 DC008072 / NIDCD NIH HHS
            • 5 T32 DC 8072-3 / NIDCD NIH HHS

            Conflict of Interest Statement

            Conflict of Interest: Authors disclose no conflict of interest.

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