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Genetica Pedigree


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AJVR, Vol 63, No. 7, July 2002 1029

Canine hip dysplasia (CHD) is a common developmental

trait that affects primarily large breed dogs

and is characterized by poor hip joint congruity, joint

laxity and subluxation, and development of secondary

coxofemoral joint osteoarthritis (OA).1-3 Hip dysplasia

is a quantitative trait, the expression of which is influenced

by genetic,3,4 nutritional,5 and possibly hormonal

factors.6 Heritability estimates for CHD range from

0.11 to 0.68.7-9 The complex pattern of inheritance of

CHD suggests that expression of the trait is controlled

by genes located at several quantitative trait loci

(QTL).10 Alleles that contribute to the development of

a complex trait such as CHD may act in an additive or

dominant fashion, and the magnitude of the effect of

an individual locus is independent of its mode of

inheritance. Development of CHD undoubtedly results

from complex interactions among multiple genetic loci

and environmental factors. Nevertheless, a few major

QTL are likely to be involved in trait expression, and a

single major locus may have a substantial influence on

this trait on the basis of biometric methods outlined by

Leighton.4

Hip dysplasia is most commonly diagnosed by

examination of ventrodorsal hip-extended radiographic

views of the pelvis. Radiographic criteria for subjective

grading of dogs on the basis of identification of

dysplastic conformational features and OA have been

proposed.11 Selective breeding programs determined on

the basis of this form of radiographic assessment have

been applied in a number of dog populations; however,

because of the modest sensitivity of this test in

immature dogs, success in reducing the prevalence of

CHD has been limited.4,9,12-14 Alternative methods for

measurement of the dysplastic phenotype include the

distraction index (DI),2,15 dorsolateral subluxation

(DLS) score,16 and radiographic determination of the

age of detection of femoral capital epiphyseal ossification

(OSS).17,18 These tests measure different features

of hip conformation and differ with respect to their

sensitivity and specificity as predictors of development

of hip joint OA in an experimental pedigree.19

Because neither the genetic potential to develop

CHD nor the carrier status of an individual dog can be

unequivocally inferred from its phenotype, selective

breeding programs determined on the basis of phenotypic

evaluation of adult dogs are likely to remain inefficient.

Genetic testing would aid breeders and

Received Oct 26, 2002.

Accepted Jan 8, 2002.

From the Department of Clinical Sciences (Bliss, Todhunter,

Hamilton, Dykes, Yeager, Gilbert), James A. Baker Institute for

Animal Health (Lust, Williams, Burton-Wurster), and Center for

Canine Genetics and Reproduction (Acland), College of Veterinary

Medicine, and Animal Breeding (Quaas) and Biometrics (Casella)

Units, College of Agricultural and Life Sciences, Cornell

University, Ithaca, NY 14853; and Department of Statistics,

University of Florida, Gainesville, FL 32611 (Casella, Wu).

Supported by a grant from the Morris Animal Foundation, NIH

grant AR36554, the Consolidated Research Program, and College

of Veterinary Medicine Unrestricted Alumni Funds.

Address for correspondence to Dr. Bliss.

Quantitative genetics of traits associated

with hip dysplasia in a canine pedigree

constructed by mating dysplastic Labrador

Retrievers with unaffected Greyhounds

Stuart Bliss, DVM; Rory J. Todhunter, BVSc, PhD; Richard Quaas, PhD; George Casella, PhD;

Rongling Wu, PhD; George Lust, PhD; Alma Jo Williams, BS; Samuel Hamilton, BVSc;

Nathan L. Dykes, DVM; Amy Yeager, DVM; Robert O. Gilbert, BVSc, MMedVet;

Nancy I. Burton-Wurster, PhD; Gregory M. Acland, DVM

Objective—To determine the genetic influence on

expression of traits associated with canine hip dysplasia.

Animals—193 dogs from an experimental canine

pedigree.

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

same groups.

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:

1029–1035)

prospective owners in selection of immature dogs that

do not carry susceptibility alleles for CHD.

Unfortunately, the molecular genetic basis of CHD is

unknown, and elucidation of the QTL that underlie

expression of a complex trait such as CHD is a formidable

task. Linkage analysis is a statistical method for

mapping and identification of QTL that has been used

extensively in experimental settings as well as for

genetic analysis of several human diseases.20,21 In veterinary

medicine, linkage analysis has led to the identification

of loci22-25

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