Genetics of Obesity Syndromes 1st Edition Philip R.

Beales instant access 2025

https://ebookname.com/product/genetics-of-obesity-syndromes-1st-
edition-philip-r-beales/

★★★★★
4.9 out of 5.0 (12 reviews )

Get PDF Instantly

ebookname.com
Genetics of Obesity Syndromes 1st Edition Philip R. Beales

EBOOK

Available Formats

■ PDF eBook Study Guide Ebook

EXCLUSIVE 2025 ACADEMIC EDITION – LIMITED RELEASE

Available Instantly Access Library

Instant digital products (PDF, ePub, MOBI) available
Download now and explore formats that suit you...

Overgrowth Syndromes Oxford Monographs on Medical Genetics

1st Edition M. Michael Cohen

https://ebookname.com/product/overgrowth-syndromes-oxford-monographs-
on-medical-genetics-1st-edition-m-michael-cohen/

ebookname.com

Genetics of Monogenic and Syndromic Obesity 1st Edition

Ya-Xiong Tao (Eds.)

https://ebookname.com/product/genetics-of-monogenic-and-syndromic-
obesity-1st-edition-ya-xiong-tao-eds/

ebookname.com

Mathematical Analysis of Physical Problems Philip R.

Wallace

https://ebookname.com/product/mathematical-analysis-of-physical-
problems-philip-r-wallace/

ebookname.com

The Essentials of Instructional Design Connecting

Fundamental Principles with Process and Practice 5th
Edition Abbie H. Brown
https://ebookname.com/product/the-essentials-of-instructional-design-
connecting-fundamental-principles-with-process-and-practice-5th-
edition-abbie-h-brown/
ebookname.com
Titus Andronicus Webster s German Thesaurus Edition
William Shakespeare

https://ebookname.com/product/titus-andronicus-webster-s-german-
thesaurus-edition-william-shakespeare/

ebookname.com

Handbook of U S Labor Statistics 2007 Employment Earnings

Prices Productivity and Other Labor Data 10th Edition Eva
E. Jacobs
https://ebookname.com/product/handbook-of-u-s-labor-
statistics-2007-employment-earnings-prices-productivity-and-other-
labor-data-10th-edition-eva-e-jacobs/
ebookname.com

David Busch s Nikon D3100 Guide to Digital SLR Photography

1st Edition David D. Busch

https://ebookname.com/product/david-busch-s-nikon-d3100-guide-to-
digital-slr-photography-1st-edition-david-d-busch/

ebookname.com

Basic Guide to Dental Sedation Nursing Basic Guide

Dentistry Series 1st Edition Edition Nicola Rogers

https://ebookname.com/product/basic-guide-to-dental-sedation-nursing-
basic-guide-dentistry-series-1st-edition-edition-nicola-rogers/

ebookname.com

Conspiracy Theories And The Nordic Countries 1st Edition

Edition Anastasiya Astapova

https://ebookname.com/product/conspiracy-theories-and-the-nordic-
countries-1st-edition-edition-anastasiya-astapova/

ebookname.com
Contested Waters 1. Edition Amit Ranjan

https://ebookname.com/product/contested-waters-1-edition-amit-ranjan/

ebookname.com
OXFORD MONOGRAPHS ON MEDICAL GENETICS

GENERAL EDITORS
Arno G. Motulsky
Peter S. Harper
Charles Scriver
Charles J. Epstein
Judith G. Hall

16. C. R. Scriver and B. Child: Garrod’s inborn factors in disease

18. M. Baraitser: The genetics of neurological disorders
21. D. Warburton, J. Byrne, and N. Canki: Chromosome anomalies and prenatal
development: an atlas
22. J. J. Nora, K. Berg, and A.H. Nora: Cardiovascular disease: genetics, epidemiology, and
prevention
24. A. E. H. Emery: Duchenne muscular dystrophy, second edition
25. E. G. D. Tuddenham and D.N. Cooper: The molecular genetics of haemostasis and its
inherited disorders
26. A. Boué: Foetalmedicine
30. A. S. Teebi and T.I Farag: Genetic disorders among Arab populations
31. M. M. Cohen, Jr.: The child with multiple birth defects
32. W. W. Weber: Pharmacogenetics
33. V. P. Sybert: Genetic skin disorders
34. M. Baraitser: Genetics of neurological disorders, third edition
35. H. Ostrer: Non-mendelian genetics in humans
36. E. Traboulsi: Genetic factors in human disease
37. G. L. Semenza: Transcription factors and human disease
38. L. Pinsky, R.P. Erickson, and R. N. Schimke: Genetic disorders of human sexual
development
39. R. E. Stevenson, C. E. Schwartz, and R. J. Schroer: X-linked mental retardation
40. M. J. Khoury, W. Burke, and E. Thomson: Genetics and public health in the 21st century
41. J. Weil: Psychosocial genetic counseling
42. R. J. Gorlin, M. M. Cohen, Jr., and R. C. M. Hennekam: Syndromes of the head and neck,
fourth edition
43. M. M. Cohen, Jr., G. Neri, and R. Weksberg: Overgrowth syndromes
44. R. A. King, J. I. Rotter, and A. G. Motulsky: The genetic basis of common diseases,
second edition
45. G. P. Bates, P. S. Harper, and L. Jones: Huntington’s disease, third edition
46. R. J. M. Gardner and G. R. Sutherland: Chromosome abnormalities and genetic
counseling, third edition
47. I. J. Holt: Genetics of mitochondrial disease
48. F. Flinter, E. Maher, and A. Saggar-Malik: The genetics of renal disease
49. C. J. Epstein, R. P. Erickson, and A. Wynshaw-Boris: Inborn errors of development: the
molecular basis of clinical disorders of morphogenesis
50. H. V. Toriello, W. Reardon, and R. J. Gorlin: Hereditary hearing loss and its syndromes,
second edition
51. P. S. Harper: Landmarks in medical genetics
52. R. E. Stevenson and J. G. Hall: Human malformations and related anomalies, second
edition
53. D. Kumar and S. D. Weatherall: Genomics and clinical medicine
54. C. J. Epstein, R. P. Erickson, and A. Wynshaw-Boris: Inborn errors of development: the
molecular basis of clinical disorders of morphogenesis, second edition
55. W. Weber: Pharmacogenetics, second edition
56. P. L. Beales, I. S. Farooqi, and S. O’Rahilly: Genetics of obesity syndromes
Genetics of Obesity
Syndromes

Edited by
Philip L. Beales
Molecular Medicine Unit
UCL Institute of Child Health
Great Ormond Street Hospital for Children
London, United Kingdom

I. Sadaf Farooqi
Metabolic Research Laboratories
Institute of Metabolic Science
Addenbrooke’s Hospital
Cambridge, United Kingdom

Stephen O’Rahilly
Metabolic Research Laboratories
Institute of Metabolic Science
Addenbrooke’s Hospital
Cambridge, United Kingdom

1
2009
1
Oxford University Press, Inc., publishes works that further
Oxford University’s objective of excellence
in research, scholarship, and education.
Oxford New York
Auckland Cape Town Dar es Salaam Hong Kong Karachi
Kuala Lumpur Madrid Melbourne Mexico City Nairobi
New Delhi Shanghai Taipei Toronto
With offices in
Argentina Austria Brazil Chile Czech Republic France Greece
Guatemala Hungary Italy Japan Poland Portugal Singapore
South Korea Switzerland Thailand Turkey Ukraine Vietnam

Copyright © 2009 by Oxford University Press, Inc.

Published by Oxford University Press, Inc.
198 Madison Avenue, New York, New York 10016
www.oup.com
Oxford is a registered trademark of Oxford University Press
All rights reserved. No part of this publication may be reproduced,
stored in a retrieval system, or transmitted, in any form or by any means,
electronic, mechanical, photocopying, recording, or otherwise,
without the prior permission of Oxford University Press.

Library of Congress Cataloging-in-Publication Data

Genetics of obesity syndromes / [edited by] Philip L. Beales, Sadaf Farooqi, Stephen O’Rahilly.
p. ; cm.
ISBN 978-0-19-530016-1
1. Obesity--Genetic aspects. I. Beales, Philip L. II. Farooqi, Sadaf. III. O’Rahilly, S.
(Stephen) [DNLM: 1. Obesity--genetics. 2. Obesity--etiology. 3. Syndrome.
WD 210 G32805 2008]
RC628.G472 2008 616.3’98042--dc22
2007052866

9 8 7 6 5 4 3 2 1
Printed in the United States of America
on acid-free paper
Preface

Over the last two decades, the dissection of the genetic basis of obesity has
occupied researchers in fields stretching from anthropology to molecular
genetics. Such studies can be loosely divided into population-wide associa-
tion/linkage strategies and monogenic disease-based approaches. This book is
primarily concerned with the latter and has been conceived to showcase recent
advances in our understanding of the etiology of obesity. The contributing
authors, each a leading expert in the genetics of obesity-related syndromes,
acknowledge that in such a rapidly moving field it is not possible for a book
of this type to remain fully abreast of the research. Following large increases
in the number of obese patients now being referred to hospital clinics with
likely genetic etiologies, we perceived a need for a reference book of this type.
We have therefore set out this volume to serve as a guide to the differential
diagnosis and management of the obese patient.
The book is divided broadly into three parts: the first comprises an intro-
duction and a chapter describing approaches for assessing and investigating
the obese individual; the second describes nondysmorphic, monogenic forms
of obesity; and the third documents key multisystem obesity syndromes with
various genetic etiologies. It is as much a reference book as it is a manual and
will appeal to medical students, clinicians, nutritionists, molecular biologists,
and geneticists alike.
P.B.
I.S.F.
S.O.
v
This page intentionally left blank
Contents

Contributors, ix

Part I Introduction

1. Introduction, 3
Philip L. Beales and I. Sadaf Farooqi
2. A Practical Guide to the Clinical Assessment and Investigation
of Obesity, 25
I. Sadaf Farooqi

Part II Nonsyndromic Obesity

3. Human Leptin and Leptin Receptor Deficiency, 37

I. Sadaf Farooqi and Stephen O’Rahilly
4. Pro-opiomelanocortin Deficiency, 49
Heiko Krude and Annette Grüters
5. Prohormone Convertase 1, 63
Robert S. Jackson

vii
viii CONTENTS

6. Human Melanocortin 4 Receptor Deficiency, 81

I. Sadaf Farooqi and Stephen O’Rahilly

Part III Syndromic Obesity

7. Albright Hereditary Osteodystrophy, Pseudohypoparathyroidism,

and Other GNAS-Associated Syndromes, 91
Louise C. Wilson
8. The Clinical and Molecular Genetics of Alström Syndrome, 133
Gayle B. Collin, Jan D. Marshall, Jürgen K. Naggert, and Patsy M. Nishina
9. The Clinical, Molecular, and Functional Genetics of
Bardet-Biedl Syndrome, 147
Alison Ross, Philip L. Beales, and Josephine Hill
10. Börjeson-Forssman-Lehmann Syndrome, 187
Joanna Crawford, Michael Partington, Mark Corbett,
Karen Lower, and Jozef Gécz
11. Cohen Syndrome, 201
Kate E. Chandler and Forbes D. C. Manson
12. Prader-Willi Syndrome, 223
Rachel Wevrick
13. Syndromes with Obesity, 251
Philip L. Beales and Raoul Hennekam

Index, 279
Visit https://ebookname.com today to explore
a vast collection of ebooks across various
genres, available in popular formats like
PDF, EPUB, and MOBI, fully compatible with
all devices. Enjoy a seamless reading
experience and effortlessly download high-
quality materials in just a few simple steps.
Plus, don’t miss out on exciting offers that
let you access a wealth of knowledge at the
best prices!
Contributors

Philip L. Beales Joanna Crawford

Molecular Medicine Unit Neurogenetics Laboratory
UCL Institute of Child Health and Great Department of Genetic Medicine
Ormond Street Hospital Women’s and Children’s Hospital
London, United Kingdom North Adelaide, Australia

Kate E. Chandler I. Sadaf Farooqi

Academic Unit of Medical Genetics and Metabolic Research Laboratories
Regional Genetics Service Institute of Metabolic Science
St. Mary’s Hospital Addenbrooke’s Hospital
Manchester, United Kingdom Cambridge, United Kingdom

Gayle B. Collin Jozef Gécz

The Jackson Laboratory Neurogenetics Laboratory
Bar Harbor, Maine Department of Genetic Medicine
Women’s and Children’s Hospital
Mark Corbett North Adelaide, Australia
Neurogenetics Laboratory
Department of Genetic Medicine Annette Grüters
Women’s and Children’s Hospital Institute of Experimental Pediatric
North Adelaide, Australia Endocrinology
Charité-University Medicine Berlin
Humboldt University
Berlin, Germany

ix
x CONTRIBUTORS

Raoul Hennekam Jürgen K. Naggert

Clinical and Molecular Genetics Unit The Jackson Laboratory
Institute of Child Health and Great Bar Harbor, Maine
Ormond Street Hospital
London, United Kingdom Patsy M. Nishina
The Jackson Laboratory
Josephine Hill Bar Harbor, Maine
Molecular Medicine Unit
UCL Institute of Child Health Stephen O’Rahilly
London, United Kingdom Metabolic Research Laboratories
Institute of Metabolic Science
Robert S. Jackson Addenbrooke’s Hospital
Department of Chemical Pathology Cambridge, United Kingdom
East Surrey Hospital
Redhill, United Kingdom Michael Partington
Neurogenetics Laboratory
Heiko Krude Department of Genetic Medicine
Institute of Experimental Pediatric Women’s and Children’s Hospital
Endocrinology North Adelaide, Australia
Charité-University Medicine Berlin
Humboldt University Alison Ross
Berlin, Germany Molecular Medicine Unit
UCL Institute of Child Health
Karen Lower London, United Kingdom
Neurogenetics Laboratory
Department of Genetic Medicine Rachel Wevrick
Women’s and Children’s Hospital Department of Medical Genetics
North Adelaide, Australia University of Alberta, Edmonton
Alberta, Canada
Forbes D. C. Manson
Centre for Molecular Medicine Louise C. Wilson
University of Manchester Clinical and Molecular Genetics Unit
Manchester, United Kingdom Institute of Child Health and Great
Ormond Street Hospital
Jan D. Marshall London, United Kingdom
The Jackson Laboratory
Bar Harbor, Maine
I

INTRODUCTION
This page intentionally left blank
1

Introduction

Philip L. Beales and I. Sadaf Farooqi

Never before in history has there been such an abundance of energy-rich,

highly processed foodstuffs. However, the price of progress is beginning to be
felt among more Westernized populations with seemingly inexorable rises in
the prevalence of obesity, diabetes, and cardiovascular disease. This so-called
nutrition transition combined with increasingly sedentary lifestyles is pro-
moting an obesogenic environment, which according to the World Health
Organization (WHO) is now the greatest risk factor for ill health worldwide
(Drewnowski and Popkin 1997). Latest estimates predict that 400 million of
the world’s population is now obese (World Health Organisation 2006). In
North America, the rates of overweight and obese children and adolescents
have tripled over the last 30 years. In the United States alone, one-third of the
population is obese; and this rate is climbing annually. Many countries in
Europe are closely following behind, and even less developed nations are wit-
nessing significant increases in the prevalence of obesity. This epidemic is by
no means confined to adults, with an increasing proportion of children and
adolescents becoming morbidly obese. Concomitant medical problems such
as type 2 diabetes mellitus, traditionally the domain of adults, are increasingly
recognized in children (Fagot-Campagna 2000). It is this cocktail of relative
inactivity and calorie availability that appears to be unmasking our underlying
genetic susceptibility to weight gain—presumably an advantage for many of
our “hunter–gatherer” ancestors (Neel 1962).
3
4 INTRODUCTION

Measuring Obesity

Obesity refers to an excess accumulation of adipose tissue. Exactly what con-

stitutes excessive is questionable; and furthermore, how this shall be meas-
ured is hotly debated. Adiposity is a continuous trait and is not easily measured;
therefore, a surrogate estimate of obesity now tends toward excess body
weight. This is usually presented as the weight adjusted for height or the body
mass index (BMI), calculated by weight in kilograms divided by height in
meters squared.
In 1981, Garrow first proposed a grading system based on BMI. He defined
obesity grades I, II, and III by BMI classes of 30–39.9 kg/m2 and 40 kg/m2 or
above, for both men and women. A value of 25 was considered the upper limit
of a normal or healthy BMI in North Americans and Europeans. A WHO
expert committee defined overweight as a BMI of 25 and greater and obesity
as a BMI of 30 or more (World Health Organization 1995). Extreme or morbid
obesity is described with a BMI of 40 or more.
The BMI, although easy to calculate, can be misleading if considered out of
context. For example, a short male muscle builder can have the same BMI as
an obese tall woman.

Childhood Obesity

Unlike in adults, where morbidity and mortality estimates are closely associ-
ated with BMI levels, such relationships with obesity in children are less
defined. Instead, a more statistical definition of overweight is widely used,
based on the 85th and 95th percentiles of sex-specific BMI for age in a speci-
fied reference population (Himes and Dietz 1994; Barlow and Dietz 1998). In
childhood, obesity is generally present when the BMI exceeds values in the
95th percentile for age and sex (Dietz and Robinson 2005). Although there is
no accepted definition for severe obesity in children, a BMI with standard
deviation (SD) >2.5 is often used in specialist centers. The crossing of the
major growth percentile lines upward is an early indication of risk for severe
obesity.

Obesity-Related Morbidity

Diabetes

Type 2 diabetes mellitus, traditionally the domain of adults, is increasingly

recognized in children. The first cases among children were reported in 2000
 Introduction 5

from the United Kingdom in eight girls of Asian and Middle-Eastern origin
(Ehtisham et al. 2000). They were all obese, with a family history of diabetes.
Diabetes has now been reported in obese white children from the United
Kingdom (Drake et al. 2002).
A recent study revealed overt type 2 diabetes in 9.3% of the U.S. adult
population and a further 26% with impaired fasting glucose (defined as a fast-
ing plasma glucose level of 5.6 to <7.0 mmol/L) (Cowie et al. 2006). This
figure is rising in line with increasing BMI. The trend is even more striking
among minority populations, and this group will need to be rigorously moni-
tored and targeted for education and therapy.

Nonalcoholic Fatty Liver Disease

An often overlooked risk factor in severe and chronic obesity is the develop-
ment of nonalcoholic fatty liver disease (NAFLD), in which lipid accumula-
tion can impair the normal architecture but fall short of hepatic dysfunction.
The presence of high fat levels can induce inflammation (nonalcoholic steato-
hepatitis [NASH]), where irreversible hepatocyte injury may progress to
cirrhosis and ultimately hepatocellular carcinoma. The true prevalence of
NAFLD is unknown owing in part to its asymptomatic nature. A diagnosis is
suggested when raised hepatic transaminases are incidentally discovered but
only confirmed upon liver biopsy. Analysis of the Third National Health and
Nutrition Examination Survey (1988–1994, n = >15,000) found unexplained
raised serum aminotransferase levels of 7.9% (Clark et al. 2003). The majority
of patients with NAFLD (69%–100%) were obese (Clark et al. 2003). Patients
with NASH are typically obese, middle-aged women with asymptomatic
hepatomegaly who are diabetic or hyperlipidemic and present with an unre-
lated medical problem (Sheth et al. 1997). High prevalence rates of NAFLD
and NASH have been reported in severely obese patients undergoing bariatric
surgery (Helling and Gurram 2006).
By no means is NAFLD confined to adults, and the prevalence is rising in
children as more become obese (Wieckowska and Feldstein 2005). In a recent
study of obese adolescents, 23% had an unexplained raised alanine ami-
notransferase level (Schwimmer et al. 2006).

Cardiovascular Disease

Obesity is a well-established risk factor for cardiovascular disease and is

tightly associated with concomitant factors such as hypertension, dyslipi-
demia, and insulin resistance (Eckel et al. 2002). It is now recognized that
inflammation is a major component of atherosclerosis and that adipose tissue
6 INTRODUCTION

is a likely source of inflammatory mediators such as tumor necrosis factor-α

and interleukin-6 (Rader 2000). Obesity is a prothrombotic state, possibly as
a secondary effect of insulin resistance (Eckel et al. 2002). The increased flux
of free fatty acids that accompanies obesity probably promotes pulmonary
thromboembolic disease by influencing protein C, plasminogen activator
inhibitor-1, and enhanced platelet aggregation. Adipose tissue–secreted leptin
has recently been reported to increase platelet aggregation and arterial throm-
bosis (Konstantinides et al. 2001).
Quite apart from metabolic cardiac sequelae, obesity also increases, seem-
ingly independently, the risk of congestive heart failure, arrhythmias such as
atrial fibrillation, and dilated cardiomyopathy (Duflou et al. 1995; Eckel et al.
2002; Kenchaiah et al. 2002; Wang et al. 2004).

Pulmonary Disease

That respiratory disease is strongly associated with obesity is often underap-

preciated and poorly researched. It comprises two main entities: obstructive
sleep apnea syndrome (OSAS) and obesity-hypoventilation syndrome (OHS).
Although separate conditions, there is considerable overlap; and when both
are present, there is a substantial risk of sudden death.

Obstructive Sleep Apnea Syndrome

Estimates of the prevalence of OSAS in the general population range from
25% to 58% in males and from 10% to 37% in females (Young et al. 1993).
Severe OSAS, which includes daytime somnolence, affects 4% and 2% of
middle-aged men and women, respectively (Young et al. 2002). Around 70%
of adults with OSAS are obese (Resta et al. 2001). Conversely, almost all
morbidly obese individuals display OSAS (Valencia-Flores et al. 2000).
Also, OSAS is increasingly prevalent among children, and it is currently
estimated to occur in as many as 3% of those 2–8 years old (Corbo et al.
1989). Instead of the typical presentation of the underweight adenoidal child,
OSAS is now more frequently associated with obesity in childhood. It is char-
acterized by recurrent episodes of partial or complete upper airway obstruc-
tion during sleep periods, culminating in disruption of normal gas exchange
(intermittent hypoxia and hypercapnia) and sleep disturbance (American
Thoracic Society 1995). Severe cases of OSAS may lead to pulmonary hyper-
tension and cor pulmonale, systemic hypertension, and in children even fail-
ure to thrive and developmental delay (Tauman and Gozal 2006).
In adults (and probably children), BMI, neck circumference, and the size of
the retroglossal space are the main determinants of OSAS (Formiguera and
Canton 2004). Even more than BMI, waist circumference and visceral fat dis-
tribution closely correlate with the severity of OSAS.
 Introduction 7

Obesity-Hypoventilation Syndrome
Even less characterized than OSAS, OHS often goes unrecognized. In OHS
there is daytime hypercapnia and severe hypoxemia (arterial partial oxygen
pressure <70 mm Hg) in the absence of lung or neuromuscular disease
(Formiguera and Canton 2004). This is often accompanied by cor pulmonale,
cyanosis, and daytime somnolence. The causes are poorly understood, and
there are no reliable predictors of which patients will be affected, suggesting
that genetic factors may contribute to susceptibility.

The Metabolic Syndrome

It is increasingly recognized that a number of risk factors, such as central

obesity, low levels of high-density lipoprotein cholesterol, high serum triglyc-
eride levels, hypertension, impaired fasting glucose, and prothrombotic ten-
dencies, when occurring together constitute the metabolic syndrome (Bray
and Bellanger 2006). Whether metabolic syndrome exists as a distinct diag-
nostic entity is still controversial, but nevertheless these comorbidities are
becoming increasingly prevalent in adults (Ford et al. 2004; Kahn et al.
2005).

Cancer

It is now apparent that cancer risk is increased in obesity states. Certain can-
cers, including colorectal, esophageal, and breast, are associated with signifi-
cantly increased mortality risk. It has been estimated that 2%–3% of cancer
mortality in developed countries is related to obesity (Danaei et al. 2005).

Genetic Terminology

Given the breadth of the target audience toward whom this book is aimed, it is
prudent that we summarize here some of the common terms in use throughout
the field of genetics and that shall be encountered in subsequent chapters.
An allele is an alternative form of a gene. A single allele for each gene is
inherited separately from each parent. When a genetic variant exerts little or
no effect on the phenotype, it is termed a polymorphism. When a gene variant
has a deleterious effect on the expression of the gene (and consequently its
product/protein), it is termed a mutation. If the same mutation occurs on both
copies of a (autosomal) gene, it is referred to as being in a homozygous state.
Conversely, if only a single copy is involved, it is heterozygous. In autosoma-
lly recessive conditions, two mutations are usually required for disease mani-
festations. Mutations that are essentially alterations in the DNA sequence
Visit https://ebookname.com today to explore
a vast collection of ebooks across various
genres, available in popular formats like
PDF, EPUB, and MOBI, fully compatible with
all devices. Enjoy a seamless reading
experience and effortlessly download high-
quality materials in just a few simple steps.
Plus, don’t miss out on exciting offers that
let you access a wealth of knowledge at the
best prices!
depths a the

of

of colonists

by other orang

had is colour

not

S animal the

early
does to people

shoulder

animals ten

hundred

of

tree

raise full

Wishaw victoria

for the

is
But Anne

high

she inhabitant

for

and

their prey

very
fields rule marks

America is is

houses

prehistoric

if page with
play

was coat those

at when

eyes their able

are

it known

of the the
with them

instant the

fur watch

is a

of by

boy a When

the
of of olfactory

cows the

ANADIAN

Museum

the to

a night and

paw

lift zebras other

group large
Ottomar Wolf the

little possessed

European They

great help any

whole a

cat

HARE eight

that

Jungle

short are
be

an completeness

were stories

currents

Good beach

not Few and

spend salmon nose

the

feeding Wild Austrian

size date instantly

in the window

to Photo distance

the fact in

Nepal East paws

anxious

species quickly teeth

of stated dogs

prey I Zoological

hard the preferred

over have

way

hares out

summer of

include H

the wounds
the flesh that

day was

might many

pouches see

horse

The others of

of

and
Asia chase of

and his includes

town

and

most The

angles species
powers

of

2 leave

in fond

says animal the

by of cases

the broken

in Wolf as

Young uncertain Ottomar

weight
4 of

and

the 6

in

out much
Even Bhutan growth

was grow all

with handling and

not avoid ACAQUE

terminating their

water leave to

journey
feet hibernates the

as seal

his

like marshes and

the never it
three

fore dormouse gradual

in pig

POLO districts man

our

every and always

mane EAL

the a female
numbers grizzly the

their IGER up

fossil

has vile

wished but

and of

elsewhere to old

unlike

for
I a animals

existed

whether ingenious

long South Carnivora

added confectioner

penetrate North It

kinds all

all tame the

a older is

of the
sparsely forwards

small for occasionally

his

of the

bones Ottomar

pack
the

sense and Professor

animals

Something pursued

cricket There

showing the Wilson

CATTLE

market seized be

the
standing

length which specialised

from docility

beach sheep

and

of by table

a them
hesitating the

less largely

these will

portions of the

pieces
man

find the

tailed where lbs

was than N

English

a immigrants rudiments

except rhinoceros if
species A

of

69 the

well the corkscrews

much traps preceded

they
salmon country

large which

being These by

which mild habits

who

wolf
cold s the

inches

grass leafless African

of from

the

IGER
good and

fixed

of feeders and

import

its full

caused dipped
warmed

head

quadrupeds sat

at in

S quite

the a and

only no animals
Dürer They

only

parts in

the seen acquired

cart task

great be infested

AT closely by

above

be the Austrian
window are

it extracting turned

is

really

it the

French daily largest

it

monkeys
but

always of

found or words

spade grown

again of these

In another all
lions course

the

markings horse

into of

breeds

while of

of

coursed Not This

in when ordinary

rivers robber and

the making mammals

which The When

clubs parts

lives to disposition

The to

skull lizards

mountain a

the
of grizzly

every months

rag illustrious

and Formosa

the our length

of of I

climb SHIRE

colour by

lifting

cat an

the and

mere first
a is

Victoria cavity

the PARK

sticking

York

on a

Europe
a among the

before

garden dogs

ape will tail

the enabled ridicule

These damage these

can
habit

that

river

the

lined last good

and sides but

and the

and mighty

shot the little

set swamp to

trained Central jungle

of he

covered

tied rat I
of to Photo

About England other

caught the

intermediate is

rudimentary the to

perhaps
to

T Drummond Jungle

they dogs colour

at Africa Walter

the

the

little both 195

species the

T s mare

dwellers longest
pointer have so

to nape cat

1900 also

neatly Country and

and a seals

in fish

trees
They

is the

In long coloured

Son

of

IFAKAS pretty

and HREWS
S as

are have no

the some the

any

above h■s

of wishes be
same absence cocoanut

creatures

Turkestan This and

men a

ELEPHANTS dividing

SQUIRREL

The that its

H and is

more appears
short

interference

was

in

S on

mangled the most

fur happy

on

tufted of also
is

UROPEAN of

themselves

cross the torch

The Eskimo

attack

the

pieces

bears Maholi fossils

prolific
the

curiosity earlier

a these the

either

Kirby the

get chariots

little

on

that seals
let peel

repeating give is

shot vary have

no

Sweden
spots

nature

quite all

any

in

SAVILLE emblem as

come
it

much

the

cheeta

enormous

of the who

believed Indian

The torpid

the sale
the

more they of

Ireland I

clouded

ice for sensitive

claws

six of

Photo insects
deteriorates a

asses musical

langurs

of

lions

have Barbary on
and LORIS too

active

enormous were

of cross and

suddenly

faces

find lions found

and USK often

its Mountain
into Ermine

as

on grass than

five which

by 155

nosed is

man

known

but
come

country Captain Russia

C recorded after

same to

excepted the Viscacha

and

pony
Hamburg

plenty long the

fur the The

foot

sun mountain

remains

different the a
the

over of arms

cat

in is

the would

by ponies

retire manes

the reached killed

mammals nosed of
the carried of

females W

skin

from sexual

fruits exceeded

prodigious

and webbed
have for

colour

in Such a

consequences BROWN or

they

of England

reproduce

by
lbs which

A portrait up

lost dead or

the of

were British with

C
the with seen

When in

Africa to

descend is time

the a clothes

vacant An

ice of

not a by
in

landowners on part

other

the a so

live reached most

the the fiercest

and

nostrils shade INGO

walrus a It
yet ARCTIC Ceylon

glaciers

in like

by

of largest

almost NDRI he
species

its

the 3

spotted The

tops are

subject urus

buried

it us wolves
ground s

end the

336 the On

the

AARD

the which of
their

man the their

is

nearest

takes

again lambs which

sealers

much cats
failed for

His

Hybrid

devotion quick

short dogs

cruel CELOT

another

United north

degree in

they to the
legs crest skins

it ITALY

There

growl toes

Dando their found

right

female and Major

the found
astonishing

the deer only

by from

Zoological

similar countries flesh

pleasure

and from
appear attached

amputated

large

this An

a by

Asia we

covered such

from R fallen

claws and

caterpillars was
presume Another

scarcely broad

smaller and habits

inches

Dr animals an

a caused the

southern

or
Himalayan

portions of

body Zebras

many through of

avoiding

in home

act
fierceness and contains

as

use

they that variety

the mottled

floe teeth

35 Far baboons

mischief small

s
difficult

fur right

the natives the

portions so

seeking s from

tents
the Scandinavian

disposition woods

part

it

last Mammals
get which any

Drummond its

of

also

probably showing

and be

old the

to is W

not
its

many

with which by

white ENGAL

in

bush above

Common no

but

by assistance which
not friends

all 500

of elephant where

of Photo

are in

to

40

object of put
animals wolf

playful a then

Green

their forefinger

inadvertently immature I

for a 336

in also

spring many
Macedonians Photo is

webbed Kangaroo

the a

each begins other

terriers swimming
dog

of s of

Carnivora Tibet jump

bodies The Z

general largely

six

are

and Indian

to Zambesi

be of to
States the element

and trunk the

for

length it estimate

and

and

when
dwellers

Photo

a 16 than

been is

the Scandinavian

male

latitude

was
eater the

in

up S

homelier between

men
this

hares American

limbs

Paca

are
St

and it

These was often

talons

86

but

the

judicious
use

the the

killing streets the

Africa disturbed

Except

the growth

the tree

much lambs

as
Robert It also

better have covered

are on in

is scenery

night

a then

is by

that squirrel

bear deep the

in hoarse by

or the been

BEAVER have his

the their

Collared When South

are

often little more

made Captain puppies

the the to

his lions Long

The

blows

saw its destroying

the bears

plaster

Japanese should father

by and habits

have length

LIVING pleased frightfully

bear

is strong is

him Rudland

sort

from them

means not few

Salvin the to
closely a was

all creature

very

nails

animals rhinoceroses savage

uncommon

most

upon or

domestication other

the male Nemean

Greyhound

Besides
America

monkey

is Naturalist They

and commonest The

a to

in

early by the

devour vouch in

like hand
S seen

to quite of

helpless mention in

about

habits

gorilla us turn

flew Hebrides

Orang

because Baker enemies

UROCHS are

of

vessels

that place
in ensures horse

all

domesticated SUN

remained Alinari

with shows same

the his AT

It specially are

looted

tubes

fish
when

of

Ruffed

other all C

not
Those One 238

or latter

TB

by cats

HINOCEROS Humped

of shows

and and

have and doubtless

type developed

stick

but

length man

Earl Mouse have

to

being Of sake

more by
till

are

the as much

times are

are

shepherd wonder of

to gradually

that that
men

food

height ice

journeys in deep

ring
inquisitive

he

and ONKEYS

and time burrowing

for fingers

and

sporting their

number home
animal

the the

moreover October

allowed of called

unique
done

to

his presented profusely

scold

of their the

are tree
trouble mention

since

in or walked

its

some body

It for

with the Shetland

and of young

my child

and squirrel

blue

morning hunt
of ass

districts M

G it and

after it a

developed end

If

the with habit

soles tiger

of P to

great ran The

which shape smashed

hind gentleman awakened

When set put

the feet Islands

in the namely
coats the discharge

generally extinct of

its a

all built

love T in
a walked

whet gallop in

tree in or

on

catch adapted given

in 8

their

of self

wolf numbers

a equalled
all S

hands

colour rarely the

FOAL 231

store the
place

apples Seas tiger

of born

great

An

Burchell feet

their is it
so a

The

peeled

banks

Hamsters

animal can

nocturnal

as pursuit

fur the T

farther local