Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex.
The unique canine breed structure makes dogs an excellent model for studying genetic diseases. Within a dog breed, linkage disequilibrium is extensive, enabling genome-wide association (GWA) with only around 15,000 SNPs and fewer individuals than in human studies. Incidences of specific diseases are elevated in different breeds, indicating that a few genetic risk factors might have accumulated through drift or selective breeding. In this study, a GWA study with 81 affected dogs (cases) and 57 controls from the Nova Scotia duck tolling retriever breed identified five loci associated with a canine systemic lupus erythematosus (SLE)-related disease complex that includes both antinuclear antibody (ANA)-positive immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA). Fine mapping with twice as many dogs validated these loci. Our results indicate that the homogeneity of strong genetic risk factors within dog breeds allows multigenic disorders to be mapped with fewer than 100 cases and 100 controls, making dogs an excellent model in which to identify pathways involved in human complex diseases.
Wilbe
Maria
M
Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, Biomedical Centre, Uppsala, Sweden.
Jokinen
Päivi
P
Truvé
Katarina
K
Seppala
Eija H
EH
Karlsson
Elinor K
EK
Biagi
Tara
T
Hughes
Angela
A
Bannasch
Danika
D
Andersson
Göran
G
Hansson-Hamlin
Helene
H
Lohi
Hannes
H
Lindblad-Toh
Kerstin
K
D000818:Animals; D000974:Antibodies, Antinuclear / Q000235:genetics; D001167:Arteritis / Q000150:complications / Q000235:genetics; D016022:Case-Control Studies; D002874:Chromosome Mapping; D003095:Collagen Diseases / Q000150:complications / Q000235:genetics; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs; D056426:Genetic Loci; D055106:Genome-Wide Association Study; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications* / Q000235:genetics*; D008581:Meningitis / Q000150:complications / Q000235:genetics; D008954:Models, Biological; D012216:Rheumatic Diseases / Q000150:complications / Q000235:genetics
D000974:Antibodies, Antinuclear