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

C.J. Finno¹  T. Famula³  M. Aleman⁵  R.J. Higgins²  J.E. Madigan⁴ 

[1] Department of Population Health and Reproduction, School of Veterinary Medicine, University of California-Davis, Davis, CA;Department of Pathology, Microbiology and Immunology, School of Veterinary Medicine, University of California-Davis, Davis, CA;Department of Animal Science, School of Veterinary Medicine, University of California-Davis, Davis, CA;Department of Medicine and Epidemiology, School of Veterinary Medicine, University of California-Davis, Davis, CA;William R. Pritchard Veterinary Medical Teaching Hospital, School of Veterinary Medicine, University of California-Davis, Davis, CA

关键词: Alpha‐tocopherol;    Equine;    Genetics;    Vitamin E;   

DOI  :  10.1111/jvim.12015

来源: Wiley

【 摘 要 】

Abstract

Background

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.

Hypothesis

NAD/EDM in the American Quarter Horse (QH) is caused by a mutation in TTPA.

Animals

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.

Procedures

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 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.

【 授权许可】

Unknown   
Copyright © 2012 by the American College of Veterinary Internal Medicine