Genome-wide association analysis of idiopathic epilepsy in the Belgian shepherd

  • PDF / 1,356,849 Bytes
  • 11 Pages / 595.276 x 790.866 pts Page_size
  • 47 Downloads / 124 Views

DOWNLOAD

REPORT


(2020) 7:12

Canine Medicine and Genetics

RESEARCH

Open Access

Genome-wide association analysis of idiopathic epilepsy in the Belgian shepherd J. M. Belanger, T. R. Famula, L. C. Gershony, M. K. Palij and A. M. Oberbauer*

Abstract Background: Idiopathic epilepsy (IE) is a common neurological disorder in the domestic dog, and is defined as repeated seizure activity having no identifiable underlying cause. Some breeds, such as the Belgian shepherd dog, have a greater prevalence of the disorder. Previous studies in this and other breeds have identified ADAM23 as a gene that confers risk of IE, although additional loci are known to exist. The present study sought to identify additional loci that influence IE in the Belgian shepherd dog. Results: Genome-wide association studies (GWAS) revealed a significant association between IE and CFA 14 (p < 1.03 E− 08) and a suggestive association on CFA 37 (p < 2.91 E− 06) in a region in linkage disequilibrium with ADAM23. Logistic regression identified a 2-loci model that demonstrated interaction between the two chromosomal regions that when combined predicted IE risk with high sensitivity. Conclusions: Two interacting loci, one each on CFAs 14 and 37, predictive of IE in the Belgian shepherd were identified. The loci are adjacent to potential candidate genes associated with neurological function. Further exploration of the region is warranted to identify causal variants underlying the association. Additionally, although the two loci were very good at predicting IE, they failed to capture all the risk, indicating additional loci or incomplete penetrance are also likely contributing to IE expression in the Belgian shepherd dog. Keywords: Idiopathic epilepsy, ADAM23, Dog, Seizures, Epilepsy, GWAS

Lay abstract Many dog breeds suffer from repeated seizure disorders. Idiopathic epilepsy, known to be inherited, is typically characterized as adult onset seizure activity with no identifiable underlying cause. Genetic association studies have been undertaken to reveal the causal DNA risk variants responsible for IE, although few significant genomic regions of association have been discovered. ADAM23, on canine chromosome 37 (CFA 37) has been identified as an IE gene common to many breeds. The present study investigated IE in the Belgian shepherd dog and found two regions of association, one on CFA 14 and a second suggestive region on CFA 37 in the vicinity of ADAM23. Using the statistical tool of logistic * Correspondence: [email protected] Department of Animal Science, University of California, One Shields Ave, Davis, CA 95616, USA

regression, the two regions were found to interact, with certain genotypes within the regions being associated with increased risk of IE in this breed.

Background Idiopathic epilepsy, or repeated seizure activity with no clear etiology, has been observed across mixed and purebred dogs [1, 2], although some breeds, such as Belgian shepherd, Irish Wolfhound, Labrador Retriever, Border Terrier, Petit Basset Griffon Vendén, Finnish Spitz, Italian Spin