Pedigree Analysis and Exclusion of Alpha‐Tocopherol Transfer Protein (TTPA) as a Candidate Gene for Neuroaxonal Dystrophy in the American Quarter Horse. (27th November 2012)

• Record Type: Journal Article
• Authors: Finno, C.J.; Famula, T.; Aleman, M.; Higgins, R.J.; Madigan, J.E.; Bannasch, D.L.
• Is Part Of: Journal of veterinary internal medicine. Volume 27:Number 1(2013:Jan./Feb.)
• Page Start: 177
• Page End: 185
• Publication Date: 2012-11-27
• Subjects: Veterinary medicine -- Periodicals; 636.0896
• DOI: 10.1111/jvim.12015
• Languages: English
• ISSNs: 0891-6640

Abstract

<abstract abstract-type="main" xml:lang="en" id="jvim12015-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="jvim12015-sec-0001" sec-type="section"> <title>Background</title> <p>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 (<italic>TTPA</italic>). To evaluate variants found upon sequencing <italic>TTPA</italic> in the horse, the mode of inheritance for NAD/EDM had to be established.</p> </sec> <sec id="jvim12015-sec-0002" sec-type="section"> <title>Hypothesis</title> <p>NAD/EDM in the American Quarter Horse (QH) is caused by a mutation in <italic>TTPA</italic>.</p> </sec> <sec id="jvim12015-sec-0003" sec-type="section"> <title>Animals</title> <p>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.</p> </sec> <sec id="jvim12015-sec-0004" sec-type="section"> <title>Procedures</title> <p>Pedigrees and genotypes across 54, 000 single nucleotide polymorphism (SNP) markers were assessed to determine heritability and mode of inheritance of NAD/EDM. <italic>TTPA</italic> sequence of exon/intron boundaries was evaluated in 2 affected and 2 control horses. An association analysis was performed by 71 SNPs surrounding <italic>TTPA</italic> and 8 SNPs within <italic>TTPA</italic> that were discovered by sequencing. RT‐PCR for <italic>TTPA</italic> was performed on mRNA from the liver of 4 affected and 4 control horses.</p> </sec> <sec id="jvim12015-sec-0005" sec-type="section"> <title>Results</title> <p>Equine NAD/EDM appears to be inherited as a polygenic trait and, within this family of QHs, demonstrates high heritability. Sequencing of <italic>TTPA</italic> identified 12 variants. No significant association was found using the 79 available variants in and surrounding <italic>TTPA</italic>. RT‐PCR yielded PCR products of equivalent sizes between affected cases and controls.</p> </sec> <sec id="jvim12015-sec-0006" sec-type="section"> <title>Conclusions and Clinical Importance</title> <p>NAD/EDM demonstrates heritability in this family of QHs. Variants in <italic>TTPA</italic> are not responsible for NAD/EDM in this study population.</p> </sec> </abstract>