Open AccessPedigree Analysis and Exclusion of Alpha‐Tocopherol Transfer Protein ( TTPA ) as a Candidate Gene for Neuroaxonal Dystrophy in the American Quarter Horse
Author(s) -
Finno C.J.,
Famula T.,
Aleman M.,
Higgins R.J.,
Madigan J.E.,
Bannasch D.L.
Publication year - 2012
Publication title -
journal of veterinary internal medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.356
H-Index - 103
eISSN - 1939-1676
pISSN - 0891-6640
DOI - 10.1111/jvim.12015
Subject(s) - genetics , single nucleotide polymorphism , allele , snp , ataxia , heritability , genotype , biology , exon , medicine , pedigree chart , gene , disease gene identification , mutation , exome sequencing , neuroscience
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) QH s 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 QH s, 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 QH s. Variants in TTPA are not responsible for NAD / EDM in this study population.