Objective—To determine the genetic influence on
expression of traits associated with canine hip dysplasia.
Animals—193 dogs from an experimental canine
Procedure—An experimental canine pedigree was
developed for linkage analysis of hip dysplasia by mating
dysplastic Labrador Retrievers with nondysplastic
Greyhounds. A statistical model was designed to test
the effects of Labrador Retriever and Greyhound alleles
on age at detection of femoral capital epiphyseal
ossification, 8-month distraction index, and 8-month
dorsolateral subluxation score.
Results—The additive effect was significant for age
at detection of femoral capital epiphyseal ossification.
Restricted maximum likelihood estimates (± SD)
for this trait were 6.4 ± 1.95, 10.2 ± 2.0, 10.8 ± 3.1,
11.4 ± 2.1, and 13.6 ± 4.6 days of age for
Greyhounds, Greyhound backcross dogs, F1 dogs,
Labrador Retriever backcross dogs, and Labrador
Retrievers, respectively. The additive effect was also
significant for the distraction index. Estimates for this
trait were 0.21 ± 0.07, 0.29 ± 0.15, 0.44 ± 0.12, 0.52
± 0.18, and 0.6 ± 0.17 for the same groups, respectively.
For the dorsolateral subluxation score, additive
and dominance effects were significant. Estimates
for this trait were 73.5 ± 4.1, 71.3 ± 6.5, 69.1 ± 6.0,
50.6 ± 12.9, and 48.4 ± 7.7%, respectively, for the
Conclusions—In this canine pedigree, traits associated
with canine hip dysplasia are heritable. Phenotypic
differences exist among founder dogs of each breed
and their crosses. This pedigree should be useful for
identification of quantitative trait loci underlying the
dysplastic phenotype. (Am J Vet Res 2002;63:
Objective—To estimate heritabilities and genetic correlations among 4 traits of hip joints (distraction index [DI], dorsolateral subluxation [DLS] score, Norberg angle [NA], and extended–hip joint radiograph [EHR] score) and to derive the breeding values for these traits in dogs.
Animals—2,716 dogs of 17 breeds (1,551 dogs in which at least 1 hip joint trait was measured).
Procedures—The NA was measured, and an EHR score was assigned. Hip joint radiographs were obtained from some dogs to allow calculation of the DI and DLS score. Heritabilities, genetic correlations, and breeding values among the DI, DLS score, NA, and EHR score were calculated by use of a set of multiple-trait, derivative-free, restricted maximum likelihood computer programs.
Results—Among 2,716 dogs, 1,411 (52%) had an estimated inbreeding coefficient of 0%; the remaining dogs had a mean inbreeding coefficient of 6.21%. Estimated heritabilities were 0.61, 0.54, 0.73, and 0.76 for the DI, DLS score, NA, and EHR score, respectively. The EHR score was highly genetically correlated with the NA (r = −0.89) and was moderately genetically correlated with the DI (r = 0.69) and DLS score (r = −0.70). The NA was moderately genetically correlated with the DI (r = −0.69) and DLS score (r = 0.58). Genetic correlation between the DI and DLS score was high (r = −0.91).
Conclusions and Clinical Relevance—Establishment of a selection index that makes use of breeding values jointly estimated from the DI, DLS score, NA, and EHR score should enhance breeding programs to reduce the incidence of hip dysplasia in dogs.
Objective—To identify the quantitative trait loci (QTL) that contribute to hip dysplasia in dogs.
Animals—192 Labrador Retrievers.
Procedures—Hip dysplasia was measured by use of the Norberg angle (NA), dorsolateral subluxation (DLS) score, and distraction index (DI). Genome-wide screening was conducted by use of 276 unique microsatellites. Linkage analysis was performed with a variance-based linear model. Logarithm of the odds (LOD) scores were reported when values were > 2.0.
Results—Canis familiaris autosomes (CFAs) 01, 02, 10, 20, 22, and 32 harbored significant QTL at LOD scores > 2.0. Among the 6 QTL, the QTL on CFA02 had not been reported to harbor QTL for hip dysplasia. The highest LOD score of 3.32 on CFA20 contributed to the second principal component of the DLS score and NA of the right hip joint. The QTL that was mapped on CFA01 (LOD score of 3.13 at 55 centimorgans) was located on the same chromosome reported to harbor a QTL for hip dysplasia in Portuguese Water Dogs and German Shepherd Dogs. In this study, CFAs 10, 20, 22, and 32 harbored QTL for hip dysplasia that have been identified in a Labrador Retriever–Greyhound pedigree and in German Shepherd Dogs.
Conclusions and Clinical Relevance—Multiple QTL were clearly involved with hip dysplasia. Identification of these QTL will enable fine-resolution mapping and subsequent assessment of candidate genes within the refined intervals to enable researchers to develop genetic screening tests and preventative and novel therapeutic regimens.
Objective—To evaluate the effects of 25% diet
restriction on life span of dogs and on markers of
Design—Paired feeding study.
Animals—48 Labrador Retrievers.
Procedures—Dogs were paired, and 1 dog in each
pair was fed 25% less food than its pair-mate from 8
weeks of age until death. Serum biochemical analyses
were performed, body condition was scored, and
body composition was measured annually until 12
years of age. Age at onset of chronic disease and
median (age when 50% of the dogs were deceased)
and maximum (age when 90% of the dogs were
deceased) life spans were evaluated.
Results—Compared with control dogs, food-restricted
dogs weighed less and had lower body fat content
and lower serum triglycerides, triiodothyronine,
insulin, and glucose concentrations. Median life span
was significantly longer for dogs in which food was
restricted. The onset of clinical signs of chronic disease
generally was delayed for food-restricted dogs.
Conclusions and Clinical Relevance—Results suggest
that 25% restriction in food intake increased
median life span and delayed the onset of signs of
chronic disease in these dogs. (J Am Vet Med Assoc
Objective—To determine whether a mutation in the fibrillin 2 gene (FBN2) is associated with canine hip dysplasia (CHD) and osteoarthritis in dogs.
Procedures—Hip conformation was measured radiographically. The FBN2 was sequenced from genomic DNA of 21 Labrador Retrievers and 2 Greyhounds, and a haplotype in intron 30 of FBN2 was sequenced in 90 additional Labrador Retrievers and 143 dogs of 6 other breeds. Steady-state values of FBN2 mRNA and control genes were measured in hip joint tissues of fourteen 8-month-old Labrador Retriever–Greyhound crossbreeds.
Results—The Labrador Retrievers homozygous for a 10-bp deletion haplotype in intron 30 of FBN2 had significantly worse CHD as measured via higher distraction index and extended-hip joint radiograph score and a lower Norberg angle and dorsolateral subluxation score. Among 143 dogs of 6 other breeds, those homozygous for the same deletion haplotype also had significantly worse radiographic CHD. Among the 14 crossbred dogs, as the dorsolateral subluxation score decreased, the capsular FBN2 mRNA increased significantly. Those dogs with incipient hip joint osteoarthritis had significantly increased capsular FBN2 mRNA, compared with those dogs without osteoarthritis. Dogs homozygous for the FBN2 deletion haplotype had significantly less FBN2 mRNA in their femoral head articular cartilage.
Conclusions and Clinical Relevance—The FBN2 deletion haplotype was associated with CHD. Capsular gene expression of FBN2 was confounded by incipient secondary osteoarthritis in dysplastic hip joints. Genes influencing complex traits in dogs can be identified by genome-wide screening, fine mapping, and candidate gene screening.