7

Genetics of Cruciate

Ligament Rupture

Lauren A. Bakerand Peter Muir

Introduction

Multiple epidemiologic factors have been iden-
tified that may influence the risk of cruciate
ligament rupture (CR) (for a full discussion, see
Chapter 14). Of these, the most important risk
factor for disease initiation is breed. Dogs of
high-risk breeds tend to present with CR at an
earlier age, and are more likely to present with
bilateral rupture (Harasen 2008; Guthrieet al.
2012). The effect of breed on CR presentation
suggests that genetic factors play a role in CR
pathogenesis. It is likely that genetic risk factors
combine with environmental modifiers such as
body condition score or neuter status to affect
expression of the CR trait. Identification of
valid genetic risk factors influencing CR may
lead to the discovery of targets for medical
intervention and aid in the development of
a predictive genetic test for the condition.
A predictive test of CR risk may be used to
screen young dogs for predisposition to the
disease. This information can then be used
to develop selective breeding strategies or to
counsel clients on environmental modifications
to minimize the impact of the clinical course of
the disease. In order to meet these goals, several

recent investigations have been conducted to

discover the genetic basis of CR.

Heritability

Statistically, heritability is defined as the pro-

portion of phenotypic variance that may be

explained by genetic variance. It may be loosely

defined as the extent to which individual

genetic differences contribute to changes in

observable phenotype. Heritability is expressed

as a number between 0.0 and 1.0. For example,

a heritability of 0.5 says that approximately 50%

of a disease risk is genetic, and the other 50%

must come from environmental influences. A

disease that is 100% genetic would have a heri-

tability of 1.

The heritability of CR has been assessed in

three high-risk breeds: the Boxer, the New-

foundland, and the Labrador Retriever (Nielen

et al. 2001; Wilkeet al. 2006; Bakeret al. 2017).

Newfoundlands have the highest prevalence of

CR compared to any other breed. A study of 411

Newfoundlands (92 cases, 319 controls) esti-

mated narrow-sense heritability derived from

an 11-generation pedigree at 0.27 (Wilkeet al.

2006). Nielenet al. (2001) reported heritability of

Advances in the Canine Cranial Cruciate Ligament, Second Edition. Edited by Peter Muir. © 2018 ACVS Foundation.
This Work is a co-publication between the American College of Veterinary Surgeons Foundation and Wiley-Blackwell.

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