Genetics of aggressive behaviour in Golden Retriever dogs

232 Pages·2006·11.52 MB·English

Genetics of aggressive behaviour in
Golden Retriever dogs

Genetica van agressief gedrag bij de Golden Retriever
(met een samenvatting in het Nederlands)

P R O E F S C H R I F T

ter verkrijging van de graad van doctor aan de Universiteit Utrecht op gezag
van de rector magnificus, prof. dr. W.H. Gispen, ingevolge het besluit van het
college voor promoties in het openbaar te verdedigen op
donderdag 27 april 2006 des middags te 4.15 uur

door

Linda van den Berg

geboren op 1 augustus 1977 te Oosterhout, Nederland
Promotor: Prof. Dr. B.A. van Oost

Co-promotoren: Dr. P.A.J. Leegwater
Dr. M.B.H. Schilder
The work presented in this thesis was performed at the Department of Clinical
Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University,
The Netherlands.

FaculteitderDiergeneeskunde
The research was financially supported by the Jubileumfonds Hoogleraren
Diergeneeskunde. Publication of the thesis was made possible by the generous
support of:

J.E.JuriaanseStichting

www.tinley.nl
Cover: The illustration on the cover depicts a fundamental question about
canine aggression: Are aggressive dogs wolves in sheep’s clothing or are they
sheep in wolves’ clothing? (Illustrations by Linda van den Berg)

Printed by: Ponsen & Looijen b.v., Wageningen

ISBN-10: 90-393-4227-X
ISBN-13: 978-90-393-4227-5

No part of this publication may be reproduced or transmitted in any form or
by any means, without written permission of the author.
Contents

Chapter 1. General introduction
1.1 Background and outline of the thesis 9
1.2 Why study canine aggression? 11
1.3 Review of the genetics of canine aggression 13

Chapter 2. Phenotype analysis
2.1 Phenotyping of aggressive behaviour in Golden Retrievers with 37
an aggression test
2.2 Phenotyping of aggressive behaviour in Golden Retrievers with 59
a questionnaire
2.3 Genetic variation in aggression related traits in Golden 97
Retrievers

Chapter 3. Molecular genetic analysis
3.1 Isolation and characterization of the canine serotonin receptor 115
1A gene (htr1A)
3.2 Isolation and characterization of the canine serotonin receptor 127
1B gene (htr1B)
3.3 Structure and variation of three canine genes involved in 143
serotonin binding and transport: the serotonin receptor 1A
gene (htr1A), serotonin receptor 2A gene (htr2A), and
serotonin transporter gene (slc6A4)
3.4 Evaluation of four genes involved in serotonin binding and 163
transport as candidates for aggression in Golden Retrievers

Chapter 4. General discussion 181

References 193
Summary 215
Samenvatting 221
Curriculum vitae and list of publications 227
Dankwoord 229

C H A P T E R 1
General introduction

1.1 Background and outline
1.1
Background and outline of the thesis

Understanding the relation between genes and behaviour is one of the most
challenging goals in neurobiology. The research described in this thesis aimed
to identify genetic variations underlying the variation in aggressive behaviour in
Golden Retriever dogs.

A Golden Retriever is by nature gentle, friendly and trustworthy at all times. He is also courageous,
intelligent, easy to train, and has a great desire to please his owner. It is a combination of these
attributes which makes him the ideal family companion or shooting dog. A Golden which shows any
sign of having too highly developed a guarding instinct, any tendency to bite, aggressiveness or
nervousness, has not the true Golden temperament. These differing faulty temperaments are hereditary
and dogs possessing them should never be bred from. Admittedly, such failings can be intensified by a
bad environment and incorrect treatment, but I maintain that there must be some inherent tendency
towards them in the dog for them to be displayed.
Tudor 1980

In spite of their friendly reputation, Golden Retrievers were the most
frequently encountered purebred dogs in a group of Dutch dogs diagnosed
with fear-motivated aggression (Galac and Knol 1997). Although this may in
part reflect the high number of Golden Retrievers in the Netherlands (Schellart
and den Hertog 1998), it is surprising to encounter many aggressive individuals
in a breed that has been selected for friendliness (Tudor 1980; http://www.
goldenretrieverclub.nl/; link accessed August 2005).
Knol and Schilder (1998a) listed characteristics of aggressive Golden
Retrievers based on descriptions provided by dog owners. In the majority of
the Goldens the provocation was approaching or touching the dog.
Threatening by the dogs was reduced to a minimum: the dogs growled while
biting instead of preceding biting. The dogs displayed a low body posture with
ears and tail down. Some dogs simultaneously expressed signs of dominance.
Some dogs were exclusively aggressive towards humans, while others also
attacked conspecifics. Although the owners considered this behaviour to be
threatening, most of them were very attached to their dog and described the
dog as friendly.
In a pilot study, Knol and colleagues (1997) analysed the genealogy of
30 aggressive Golden Retrievers and 66 randomly chosen dogs of the same
breed. The total group of 96 dogs appeared to consist of two familial sub-
9
Chapter 1: General introduction
groups. The number of aggressive individuals differed significantly between
these two subgroups (p=0.035). This was a first indication that genetic factors
are important in the aetiology of aggression in Golden Retrievers.
Our studies of the genetics of aggression in Goldens started in 1997. In
section 1.2 we argue why it is important to study aggression in dogs. Section
1.3 contains a review of the literature on the genetics of canine aggression.
From 1997 to 2005, dogs were recruited by approaching owners of aggressive
Golden Retrievers through advertisements in magazines for veterinarians,
Golden Retriever breeders, or dog owners (Knol and Schilder 1998a; 1998b;
1999; and 2000; van den Berg et al. 2002; 2003; 2004a; 2004b; 2005;
http://home.hccnet.nl/b.vanoost/). We collected behavioural information and
DNA samples of 139 aggressive Golden Retrievers (“probands’). We asked
owners of relatives of these probands to participate in our study as well. In
2005 we had behavioural information and a DNA sample of 138 relatives of 36
of the probands. A selection of the Golden Retriever families is depicted in the
Appendix of section 3.4 (page 175-178).
Correct phenotyping is the key to success of genetic studies (Bearden et
al. 2004; Mills 2003; Smoller et al. 1998). This is the theme of chapter 2 of this
thesis. We initially phenotyped the dogs with a behavioural (aggression) test
and a personal interview with the dog owner. In section 2.1, we describe the
analysis of aggression tests of 83 Golden Retrievers. We expected the
aggression test to provide objective and detailed behavioural phenotypes.
However, it turned out to be difficult to elicit aggressive behaviour in the test.
We therefore designed a mail questionnaire based on the successful canine
behavioural assessment and research questionnaire (Hsu and Serpell 2003). All
dog owners that had participated in our project earlier were asked to fill out the
questionnaire. The results of this survey are described in section 2.2. In section
2.3 we describe a quantitative genetic assessment of the questionnaire scores.
The aim of this work was to examine the usefulness of the behavioural
measures for genetic studies. Based on the results, we made a selection of dogs
for the molecular genetic studies presented in chapter 3.
We used a candidate gene approach in our search for molecular genetic
variants that contribute to aggression in Golden Retrievers. Four genes of the
canine serotonergic system were cloned, characterised, and studied in Golden
Retrievers (sections 3.1, 3.2, and 3.3). We studied the serotonin receptor genes
1A, 1B, and 2A (htr1A, htr1B, htr2A) and the serotonin transporter gene
(slc6A4). In section 3.4, we describe the analysis of these genes in related
Golden Retrievers. We conclude that the candidate genes are not likely to play
a major role in the variation in aggression in the Golden Retrievers. The thesis
ends with a general discussion of the results (chapter 4).
10