Pedigree Analysis and Exclusion of Alpha-Tocopherol Transfer Protein (TTPA) as a Candidate Gene for Neuroaxonal Dystrophy in the American Quarter Horse
Version of Record online: 27 NOV 2012
Copyright © 2012 by the American College of Veterinary Internal Medicine
Journal of Veterinary Internal Medicine
Volume 27, Issue 1, pages 177–185, January/February 2013
How to Cite
Finno, C.J., Famula, T., Aleman, M., Higgins, R.J., Madigan, J.E. and Bannasch, D.L. (2013), Pedigree Analysis and Exclusion of Alpha-Tocopherol Transfer Protein (TTPA) as a Candidate Gene for Neuroaxonal Dystrophy in the American Quarter Horse. Journal of Veterinary Internal Medicine, 27: 177–185. doi: 10.1111/jvim.12015
- Issue online: 11 JAN 2013
- Version of Record online: 27 NOV 2012
- Manuscript Accepted: 9 OCT 2012
- Manuscript Revised: 19 SEP 2012
- Manuscript Received: 9 APR 2012
- Vitamin E
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.
NAD/EDM in the American Quarter Horse (QH) is caused by a mutation in TTPA.
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.
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.
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 and Clinical Importance
NAD/EDM demonstrates heritability in this family of QHs. Variants in TTPA are not responsible for NAD/EDM in this study population.