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Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex
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Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex
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Journal Article
Genome-wide association mapping identifies multiple loci for a canine SLE-related disease complex
2010
Overview
Kerstin Lindblad-Toh and colleagues use genome-wide association mapping to identify risk loci for a canine systemic lupus erythematosus-related disease complex in Nova Scotia duck tolling retrievers. The study illustrates the power of using dog breeds for complex trait mapping.
The unique canine breed structure makes dogs an excellent model for studying genetic diseases. Within a dog breed, linkage disequilibrium is extensive
1
,
2
, enabling genome-wide association (GWA) with only around 15,000 SNPs and fewer individuals than in human studies
1
,
3
. 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.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Animal Genetics and Genomics
/ Animals
/ Antibodies, Antinuclear - genetics
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Collagen Diseases - complications
/ Collagen Diseases - genetics
/ Disease
/ Dogs
/ Fundamental and applied biological sciences. Psychology
/ Genetics
/ Genetics of eukaryotes. Biological and molecular evolution
/ Genome-Wide Association Study
/ Genomes
/ Humans
/ letter
/ Lupus Erythematosus, Systemic - complications
/ Lupus Erythematosus, Systemic - genetics
/ Rheumatic Diseases - complications
/ Rheumatic Diseases - genetics
