title: Complex disease and phenotype mapping in the domestic dog.
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.
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Jessica J
authors.initials: JJ
authors.lastname: Hayward
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Marta G
authors.initials: MG
authors.lastname: Castelhano
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Oliveira
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Corey
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Cheryl
authors.initials: C
authors.lastname: Balkman
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Tara L
authors.initials: TL
authors.lastname: Baxter
authors.affiliation: School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Margret L
authors.initials: ML
authors.lastname: Casal
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Center
authors.affiliation: College of Animal Science and Technology, China Agricultural University, Beijing 100094, China.
authors.forename: Meiying
authors.initials: M
authors.lastname: Fang
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Garrison
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Kalla
authors.affiliation: Department of Biological Statistics and Computational Biology, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Korniliev
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Kotlikoff
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: N S
authors.initials: NS
authors.lastname: Moise
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Shannon
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Simpson
authors.affiliation: Biology Department, La Sierra University, Riverside, California 92505, USA.
authors.forename: Nathan B
authors.initials: NB
authors.lastname: Sutter
authors.affiliation: Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Rory J
authors.initials: RJ
authors.lastname: Todhunter
authors.affiliation: Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York 14853, USA.
authors.forename: Adam R
authors.initials: AR
authors.lastname: Boyko
mesh_terms: D000818:Animals; D049628:Body Size; D004283:Dog Diseases / Q000235:genetics*; D004285:Dogs / Q000145:classification / Q000235:genetics* / Q000254:growth & development; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D010641:Phenotype; D040641:Quantitative Trait Loci