Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex.

Abstract

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.

• Authors: Maria Wilbe, Päivi Jokinen, Katarina Truvé, Eija H Seppala, Elinor K Karlsson, Tara Biagi, Angela Hughes, Danika Bannasch, Göran Andersson, Helene Hansson-Hamlin, Hannes Lohi, Kerstin Lindblad-Toh
• Journal: Nature genetics (Nat Genet) Vol. 42 Issue 3 Pg. 250-4 (Mar 2010) ISSN: 1546-1718 [Electronic] United States
• PMID: 20101241 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Validation Study)

Chemical References

• Antibodies, Antinuclear

Topics

• Animals
• Antibodies, Antinuclear (genetics)
• Arteritis (complications, genetics)
• Case-Control Studies
• Chromosome Mapping
• Collagen Diseases (complications, genetics)
• Dog Diseases (genetics)
• Dogs
• Genetic Loci
• Genome-Wide Association Study
• Humans
• Lupus Erythematosus, Systemic (complications, genetics)
• Meningitis (complications, genetics)
• Models, Biological
• Rheumatic Diseases (complications, genetics)