Genetica Pedigree
Enviado por vtgyuu • 27 de Febrero de 2014 • 5.375 Palabras (22 Páginas) • 317 Visitas
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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