Identification of quantitative trait loci for osteoarthritis of hip joints in dogs

Mateescu, Raluca G.; Burton‐Wurster, Nancy; Tsai, Kate L.; Phavaphutanon, Janjira; Zhang, Zhiwu; Murphy, Keith E.; Lust, George; Todhunter, Rory J.

doi:10.2460/ajvr.69.10.1294

Cited by 24 publications

(24 citation statements)

References 30 publications

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“…Linkage was found to hip OA in the Labrador retriever cross breed pedigree [49] but a significant association in the current GWAS was not discovered in the linked regions. The hip OA (acetabular osteophytes) locus reported on CFA03 in Portuguese Water Dogs was between ∼42 and 46 Mb [50] which was far from the SNP locus we reported at ∼74 Mb for HD.…”

Section: Discussioncontrasting

confidence: 64%

Differential Genetic Regulation of Canine Hip Dysplasia and Osteoarthritis

et al. 2010

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BackgroundCanine hip dysplasia (HD) is a common polygenic trait characterized by hip malformation that results in osteoarthritis (OA). The condition in dogs is very similar to developmental dysplasia of the human hip which also leads to OA.Methodology/Principal FindingsA total of 721 dogs, including both an association and linkage population, were genotyped. The association population included 8 pure breeds (Labrador retriever, Greyhounds, German Shepherd, Newfoundland, Golden retriever, Rottweiler, Border Collie and Bernese Mountain Dog). The linkage population included Labrador retrievers, Greyhounds, and their crosses. Of these, 366 dogs were genotyped at ∼22,000 single nucleotide polymorphism (SNP) loci and a targeted screen across 8 chromosomes with ∼3,300 SNPs was performed on 551 dogs (196 dogs were common to both sets). A mixed linear model approach was used to perform an association study on this combined association and linkage population. The study identified 4 susceptibility SNPs associated with HD and 2 SNPs associated with hip OA.Conclusion/SignificanceThe identified SNPs included those near known genes (PTPRD, PARD3B, and COL15A1) reported to be associated with, or expressed in, OA in humans. This suggested that the canine model could provide a unique opportunity to identify genes underlying natural HD and hip OA, which are common and debilitating conditions in both dogs and humans.

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Section: Discussioncontrasting

confidence: 64%

Differential Genetic Regulation of Canine Hip Dysplasia and Osteoarthritis

et al. 2010

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“…The full dataset is derived from genomic analysis of 237 DNA samples, with 25 founder individuals (15 male, 10 female, pedigree structure shown in Supplemental Material, Figure S1) from a colony of Labrador Retriever and Greyhound crosses maintained at Cornell University for over 30 yr (Todhunter et al 2003; Mateescu et al 2008; Phavaphutanon et al 2009). Genotyping was performed using genomic DNA as described in Hayward et al (2016) using Illumina CanineHD BeadChips that include more than 170,000 SNPs.…”

Section: Methodsmentioning

confidence: 99%

A Pedigree-Based Map of Recombination in the Domestic Dog Genome

Campbell

Bhérer

Morrow

et al. 2016

G3 Genes|Genomes|Genetics

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Meiotic recombination in mammals has been shown to largely cluster into hotspots, which are targeted by the chromatin modifier PRDM9. The canid family, including wolves and dogs, has undergone a series of disrupting mutations in this gene, rendering PRDM9 inactive. Given the importance of PRDM9, it is of great interest to learn how its absence in the dog genome affects patterns of recombination placement. We have used genotypes from domestic dog pedigrees to generate sex-specific genetic maps of recombination in this species. On a broad scale, we find that placement of recombination events in dogs is consistent with that in mice and apes, in that the majority of recombination occurs toward the telomeres in males, while female crossing over is more frequent and evenly spread along chromosomes. It has been previously suggested that dog recombination is more uniform in distribution than that of humans; however, we found that recombination in dogs is less uniform than in humans. We examined the distribution of recombination within the genome, and found that recombination is elevated immediately upstream of the transcription start site and around CpG islands, in agreement with previous studies, but that this effect is stronger in male dogs. We also found evidence for positive crossover interference influencing the spacing between recombination events in dogs, as has been observed in other species including humans and mice. Overall our data suggests that dogs have similar broad scale properties of recombination to humans, while fine scale recombination is similar to other species lacking PRDM9.

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“…A more powerful approach to investigate the apparent genetic complexity of CM is quantitative trait loci (QTL) analysis which aims at identifying genes or QTL that determine the disease even though each gene contributes only a small fraction. In fact, QTL analysis has been successfully used in dogs to identify QTLs associated with complex diseases like hip dysplasia or epilepsy demonstrating its power in such genetic investigation studies [12]–[14].…”

Section: Introductionmentioning

confidence: 99%

Quantitative Trait Loci (QTL) Study Identifies Novel Genomic Regions Associated to Chiari-Like Malformation in Griffon Bruxellois Dogs

Lemay

Knowler²,

Bouasker

et al. 2014

PLoS ONE

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Chiari-like malformation (CM) is a developmental abnormality of the craniocervical junction that is common in the Griffon Bruxellois (GB) breed with an estimated prevalence of 65%. This disease is characterized by overcrowding of the neural parenchyma at the craniocervical junction and disturbance of cerebrospinal fluid (CSF) flow. The most common clinical sign is pain either as a direct consequence of CM or neuropathic pain as a consequence of secondary syringomyelia. The etiology of CM remains unknown but genetic factors play an important role. To investigate the genetic complexity of the disease, a quantitative trait locus (QTL) approach was adopted. A total of 14 quantitative skull and atlas measurements were taken and were tested for association to CM. Six traits were found to be associated to CM and were subjected to a whole-genome association study using the Illumina canine high density bead chip in 74 GB dogs (50 affected and 24 controls). Linear and mixed regression analyses identified associated single nucleotide polymorphisms (SNPs) on 5 Canis Familiaris Autosomes (CFAs): CFA2, CFA9, CFA12, CFA14 and CFA24. A reconstructed haplotype of 0.53 Mb on CFA2 strongly associated to the height of the cranial fossa (diameter F) and an haplotype of 2.5 Mb on CFA14 associated to both the height of the rostral part of the caudal cranial fossa (AE) and the height of the brain (FG) were significantly associated to CM after 10 000 permutations strengthening their candidacy for this disease (P = 0.0421, P = 0.0094 respectively). The CFA2 QTL harbours the Sall-1 gene which is an excellent candidate since its orthologue in humans is mutated in Townes-Brocks syndrome which has previously been associated to Chiari malformation I. Our study demonstrates the implication of multiple traits in the etiology of CM and has successfully identified two new QTL associated to CM and a potential candidate gene.

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Identification of quantitative trait loci for osteoarthritis of hip joints in dogs

Cited by 24 publications

References 30 publications

Differential Genetic Regulation of Canine Hip Dysplasia and Osteoarthritis

Differential Genetic Regulation of Canine Hip Dysplasia and Osteoarthritis

A Pedigree-Based Map of Recombination in the Domestic Dog Genome

Quantitative Trait Loci (QTL) Study Identifies Novel Genomic Regions Associated to Chiari-Like Malformation in Griffon Bruxellois Dogs

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