Complex disease and phenotype mapping in the domestic dog

Jessica J. Hayward, Marta G. Castelhano, Kyle C. Oliveira, Elizabeth Corey, Cheryl Balkman, Tara L. Baxter, Margret L. Casal, Sharon A. Center, Meiying Fang, Susan J. Garrison, Sara E. Kalla, Pavel Korniliev, Michael I. Kotlikoff, N. S. Moise, Laura M. Shannon, Kenneth W. Simpson, Nathan B. Sutter, Rory J. Todhunter and Adam R. Boyko ()
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Jessica J. Hayward: College of Veterinary Medicine, Cornell University
Marta G. Castelhano: College of Veterinary Medicine, Cornell University
Kyle C. Oliveira: College of Veterinary Medicine, Cornell University
Elizabeth Corey: College of Veterinary Medicine, Cornell University
Cheryl Balkman: College of Veterinary Medicine, Cornell University
Tara L. Baxter: College of Veterinary Medicine, Cornell University
Margret L. Casal: School of Veterinary Medicine, University of Pennsylvania
Sharon A. Center: College of Veterinary Medicine, Cornell University
Meiying Fang: College of Animal Science and Technology, China Agricultural University
Susan J. Garrison: College of Veterinary Medicine, Cornell University
Sara E. Kalla: College of Veterinary Medicine, Cornell University
Pavel Korniliev: Cornell University
Michael I. Kotlikoff: College of Veterinary Medicine, Cornell University
N. S. Moise: College of Veterinary Medicine, Cornell University
Laura M. Shannon: College of Veterinary Medicine, Cornell University
Kenneth W. Simpson: College of Veterinary Medicine, Cornell University
Nathan B. Sutter: La Sierra University
Rory J. Todhunter: College of Veterinary Medicine, Cornell University
Adam R. Boyko: College of Veterinary Medicine, Cornell University

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract The domestic dog is becoming an increasingly valuable model species in medical genetics, showing particular promise to advance our understanding of cancer and orthopaedic disease. Here we undertake the largest canine genome-wide association study to date, with a panel of over 4,200 dogs genotyped at 180,000 markers, to accelerate mapping efforts. For complex diseases, we identify loci significantly associated with hip dysplasia, elbow dysplasia, idiopathic epilepsy, lymphoma, mast cell tumour and granulomatous colitis; for morphological traits, we report three novel quantitative trait loci that influence body size and one that influences fur length and shedding. Using simulation studies, we show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate- to large-effect complex disease loci. This proposed design will enable efficient mapping of canine complex diseases, most of which have human homologues, using far fewer samples than required in human studies.

Date: 2016
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DOI: 10.1038/ncomms10460

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