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.
Highlights
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
Using genome-wide association studies (GWAS) on the 12 most common recorded phenotypes, we find loci associated with several canine complex diseases (including hip dysplasia, granulomatous colitis (GC) and idiopathic epilepsy), as well as novel loci affecting morphological traits, namely body size, fur length and shedding
Using a univariate linear mixed model implemented in the program GEMMA25, we conducted across-breed GWAS for the diseases CHD, ED, CCLD, lymphoma, PSVA, MCT and MVD, and within-breed GWAS for idiopathic epilepsy in Irish Wolfhounds, GC in Boxers and Bulldogs, lymphoma in Golden Retrievers, MCT in Labrador Retrievers, and PSVA in Yorkshire Terriers
Summary
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. We show that modestly larger sample sizes and denser marker sets will be sufficient to identify most moderate- to large-effect complex disease loci. Small founder populations and selective breeding have resulted in long regions of linkage disequilibrium (LD) within breeds—over 1 Mb—while across breeds LD is much shorter, more similar to that seen in humans[2,3] This unique breed structure has facilitated the fine mapping of nearly 200 Mendelian traits and disorders, including narcolepsy and cataracts[4,5], using much smaller sample sizes than required in human disease association studies. The current canine mapping array of 173,000 markers has sufficient power to detect large-effect alleles (Z2-fold risk increase) with 100 cases and 100 controls from a single breed[6]. Larger cohorts of individually phenotyped dogs across multiple breeds are needed to identify the genetic risk factors missed by previous mapping efforts, and provide a better understanding of the genetic architecture underlying complex phenotypes in the dog
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
