| Summary: | Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is an inherited neurodegenerative disorder of unknown etiology. Clinical signs of neurological deficits develop within the first year of life in vitamin E (vitE) deficient horses. A genome-wide association study (GWAS) was carried out using 670,000 SNP markers in 27 case and 42 control Quarter Horses. Two markers, encompassing a 2.5 Mb region on ECA7, were associated with the phenotype (<i>p</i> = 2.05 × 10<sup>-7</sup> and 4.72 × 10<sup>-6</sup>). Within this region, caytaxin (<i>ATCAY</i>) was identified as a candidate gene due to its known role in Cayman Ataxia and ataxic/dystonic phenotypes in mouse models. Whole-genome sequence data in four eNAD/EDM and five unaffected horses identified 199 associated variants within the ECA7 region. MassARRAY<sup>®</sup> genotyping was performed on these variants within the GWAS population. The three variants within <i>ATCAY</i> were not concordant with the disease phenotype. No difference in expression or alternative splicing was identified using qRT-PCR in brainstem across the <i>ATCAY</i> transcript. <i>Atcay<sup>ji</sup></i><sup>-hes</sup> mice were then used to conduct functional analysis in a second animal model. Histologic lesions were not identified in the central nervous system of <i>Atcay<sup>ji</sup></i><sup>-hes</sup> mice. Additionally, supplementation of homozygous <i>Atcay<sup>ji</sup></i><sup>-hes</sup> mice with 600 IU/day of dl-α-tocopheryl acetate (vitE) during gestation, lactation, and adulthood did not improve the phenotype. <i>ATCAY</i> has therefore been excluded as a candidate gene for eNAD/EDM.
|
|---|
