Open AccessGenetics of Hereditary Ataxia in Scottish Terriers
Author(s) -
Urkasemsin G.,
Nielsen D.M.,
Singleton A.,
Arepalli S.,
Hernandez D.,
Agler C.,
Olby N.J.
Publication year - 2017
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.14738
Subject(s) - ataxia , medicine , disease gene identification , cerebellar ataxia , genetics , disease , genetic linkage , pediatrics , mutation , pathology , biology , exome sequencing , psychiatry , gene
Background Scottish Terriers have a high incidence of juvenile onset hereditary ataxia primarily affecting the Purkinje neuron of the cerebellar cortex and causing slowly progressive cerebellar dysfunction. Objective To identify chromosomal regions associated with hereditary ataxia in Scottish Terriers. Animals One hundred and fifty‐three Scottish Terriers were recruited through the Scottish Terrier Club of America. Materials and Methods Prospective study. Dogs were classified as affected if they had slowly progressive cerebellar signs. When possible, magnetic resonance imaging and histopathological evaluation of the brain were completed as diagnostic aids. To identify genomic regions connected with the disease, genome‐wide mapping was performed using both linkage‐ and association‐based approaches. Pedigree evaluation and homozygosity mapping were also performed to examine mode of inheritance and to investigate the region of interest, respectively. Results Linkage and genome‐wide association studies in a cohort of Scottish Terriers both identified a region on CFA X strongly associated with the disease trait. Homozygosity mapping revealed a 4 Mb region of interest. Pedigree evaluation failed to identify the possible mode of inheritance due to the lack of complete litter information. Conclusion and Clinical Importance This finding suggests that further genetic investigation of the potential region of interest on CFA X should be considered in order to identify the causal mutation as well as develop a genetic test to eliminate the disease from this breed.