Genetics and sports

208 Pages·2009·1.11 MB·English

by  Collins M. (ed.)

Genetics and Sports
Medicine and Sport Science
Vol. 54
Series Editors
J. Borms
Brussels
M. Hebbelinck
Brussels
A.P. Hills
Brisbane
T. Noakes
Cape Town
Genetics and Sports
Volume Editor
Malcolm Collins
Cape Town
11 figures, and 12 tables, 2009
Basel · Freiburg · Paris · London · New York · Bangalore ·
Bangkok · Shanghai · Singapore · Tokyo · Sydney
Medicine and Sport Science
Founded 1968 by E. Jokl, Lexington, Ky.
Malcolm Collins, PhD
MRC/UCT Research Unit for Exercise Science and Sports Medicine (ESSM)
South African Medical Research Council (MRC) and the
Department of Human Biology, University of Cape Town (UCT)
Sports Science Institute of South Africa
Boundary Road
Newlands 7700, Cape Town (South Africa)
This book was generously supported by
Library of Congress Cataloging-in-Publication Data
Genetics and sports / volume editor, Malcolm Collins.
p. ; cm. -- (Medicine and sport science, ISSN 0254-5020 ; v. 54)
Includes bibliographical references and indexes.
ISBN 978-3-8055-9027-3 (hard cover : alk. paper)
1. Sports--Physiological aspects. 2. Human genetics. I. Collins,
Malcolm, 1965- II. Series: Medicine and sport science, v. 54. 0254-5020 ;
[DNLM: 1. Genetic Phenomena. 2. Sports. 3. Athletic Injuries--genetics.
4. Athletic Performance--physiology. 5. Exercise--physiology. 6. Genetic
Techniques. W1 ME649Q v.54 2009 / QT 260 G3285 2009]
RC1235.G46 2009
599.93(cid:2)5--dc22
2009024000
Bibliographic Indices. This publication is listed in bibliographic services, including Current Contents® and Index Medicus.
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© Copyright 2009 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland)
www.karger.com
Printed in Switzerland on acid-free and non-aging paper (ISO 9706) by Reinhardt Druck, Basel
ISSN 0254–5020
ISBN 978–3–8055–9027–3
e-ISBN 978–3–8055–9028–0
Contents
VII Preface
Collins, M. (Cape Town)
1 Key Concepts in Human Genetics: Understanding the Complex Phenotype
Gibson, W.T. (Vancouver, B.C.)
11 Nature versus Nurture in Determining Athletic Ability
Brutsaert, T.D. (Albany, N.Y.); Parra, E.J. (Mississauga Ont.)
28 Genetics and Sports: An Overview of the Pre-Molecular Biology Era
Peeters, M.W. (Leuven/Brussels); Thomis, M.A.I.; Beunen, G.P. (Leuven);
Malina, R.M. (Austin, Tex./Stephenville, Tex.)
43 Genes, Athlete Status and Training – An Overview
Ahmetov, I.I. (St. Petersburg/Moscow); Rogozkin, V.A. (St. Petersburg)
72 Angiotensin-Converting Enzyme, Renin-Angiotensin System and Human
Performance
Woods, D. (Newcastle upon Tyne)
88 α-Actinin-3 and Performance
Yang, N.; Garton, F.; North, K. (Sydney, NSW)
102 East African Runners: Their Genetics, Lifestyle and Athletic Prowess
Onywera, V.O. (Nairobi)
110 Gene-Lifestyle Interactions and Their Consequences on Human Health
Pomeroy, J. (Phoenix, Ariz./Umeå); Söderberg, A.M.; Franks, P.W. (Umeå)
136 Genetic Risk Factors for Musculoskeletal Soft Tissue Injuries
Collins, M. (Cape Town); Raleigh, S.M. (Northampton)
150 Innovative Strategies for Treatment of Soft Tissue Injuries in Human and
Animal Athletes
Hoffmann, A.; Gross, G. (Braunschweig)
166 Gene Doping: Possibilities and Practicalities
Wells, D.J. (London)
V
176 Genetic Testing of Athletes
Williams, A.G. (Alsager); Wackerhage, H. (Aberdeen)
187 The Future of Genetic Research in Exercise Science and Sports Medicine
Trent, R.J.; Yu, B. (Camperdown, NSW)
196 Author Index
197 Subject Index
VI Contents
Preface
Athletic performance and the occurrence of sports-related injuries are both multifac-
torial conditions which are determined by the complex and poorly understood inter-
actions of both environmental and genetic factors. Although much work has been
done to identify the non-genetic components that are associated with performance
and susceptibility to injuries, there is an ever growing body of research investigating
the genetic contribution to these phenotypes. This book, which contains contribu-
tions by a broad range of scientist and clinicians from several disciplines – including,
but not limited to, human molecular genetics, clinical genetics and exercise science –
covers a number of topics in an attempt to obtain an integrated and holistic under-
standing of the field. The recent sequencing of the human genome and development
of several tools and methodologies have successfully been used to investigate the
genetic contribution to many complex diseases. This area of research has more
recently been applied to the fields of exercise science and sports medicine. This pub-
lication reviews past, current and future applications, as well as the ethical concerns,
of genetic research in the fields of exercise science and sports medicine.
The introductory chapter of this book highlights current and key concepts in
human genetics, in particular with respect to its application to understanding multi-
factorial conditions. This is followed by a chapter exploring the often misunderstood
relationship between nature (genetics) and nurture (common environmental effects
such as training, diet, etc.) in determining athletic ability. The third chapter sum-
marises the methodologies initially used during the pre-molecular biology era and
the estimates obtained for gene and environmental contributions for performance-
related phenotypes. The molecular genetics of performance is specifically investi-
gated in the subsequent four chapters. These chapters include a review of the specific
DNA sequence variants currently believed to be associated with athletic performance
and response to training, critical reviews of the roles of the much investigated variants
within the angiotensin-converting enzyme and α-actinin-3 genes and performance,
and finally an exploration of the genetic and lifestyle of the East African runners who
have dominated distance running events for the last half century.
VII
This book also contains a chapter exploring the interaction of lifestyle, such as
physical active or sedentary, with genetic make-up and its implications on human
health, in particular understanding mechanisms underlying specific diseases, such as
obesity, and its prevention. This is followed by a chapter summarising the recent
developments in the identification of genetic risk factors for musculoskeletal soft tis-
sue injuries.
The current and possible application of gene therapy as well as other novel thera-
peutic strategies such as stem cell and growth factor therapies in injured athletes is
also reviewed. This is followed by a chapter exploring the potential abuse of genetic
information and technologies, together with other developments in molecular biol-
ogy, (gene doping) to enhance performance. The ethical framework in which genetic
research is done and its application is not straightforward. Exercise scientists and
sports physicians need to keep abreast of advances in medical ethics broadly and cus-
tomise them efficiently to the field. These issues are discussed in the second last chap-
ter, which is followed by a review on the new technologies and paradigms which will
influence future genetic research in exercise science and sports medicine.
Malcolm Collins, Cape Town
VIII Preface
Collins M (ed): Genetics and Sports.
Med Sport Sci. Basel, Karger, 2009, vol 54, pp 1–10
Key Concepts in Human Genetics:
Understanding the Complex Phenotype
William T. Gibson
Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver,
B.C., Canada
Abstract
The recent sequencing of a reference human genome has generated a large number of DNA-based
tools, which are being used to locate genes that contribute to disease. These tools have also enabled
studies of the genetics of non-disease traits such as athletic fitness. Sport scientists should keep in
mind three major factors when designing such studies and interpreting the literature. First of all, the
methods used to assign a biological trait (be it performance related or disease related) to a specific
gene are not as powerful as is commonly believed. Second, the methods used are thought to be
more robust for disease-related traits than for normal physical characteristics, likely because there
are many more biological factors contributing to the latter. Third, additional levels of variability con-
tinue to be uncovered in the human genome; these may ultimately contribute more to physical dif-
ferences between human beings than the levels studied over the past decade. This introductory
chapter will aim to equip the reader with the necessary vocabulary to understand and interpret
genetic studies targeted to sport fitness and sport-related injury. Copyright © 2009 S. Karger AG, Basel
Key Genetic Concepts and Terms
Since the earliest days of competitive sport, athletes and their trainers have known that
athletic performance is modifiable by dedicated training. However, some individuals
appear to be naturally gifted with athletic ability, such that their performance prior to
training is above average, and their performance after training is consistently excel-
lent. Often encapsulated as the ‘nature vs. nurture debate’, the degree to which athletic
ability is determined by inherited physical characteristics, as opposed to training-and
diet-based regimens, has excited much interest.
The identification of genes that encode discrete biological molecules opened a new
avenue of investigation – that of correlating physical traits with differences between
individuals in DNA sequence. In many cases, it is easy to see how a physical trait such
as height might impact on athletic performance: longer legs allow for greater distance
to be covered with each stride. Increased cardiac output or increased lung capacity
(relative to overall body size) would similarly be predicted to enhance athletic perfor-
mance. The rapid growth in tools for DNA analysis has allowed researchers to identify
an increasingly diverse number of genes and genetic markers, and in turn to correlate
these with physical characteristics.
The biological information necessary to form all tissues of the human body is
contained in the fertilized egg. Most of this information is physically located in the
nucleus of the cell, though some is contained within energy-processing mitochon-
dria. As the fertilized egg divides, the DNA that carries this information is copied
and redistributed throughout the new cells as they are made. The term gene is used
to refer to a discrete sequence of DNA that produces a biologically active product.
If different sequences of the same gene coexist in a population, that gene is said to
have different forms termed alleles. An allele is a variant sequence of an identified
gene. Persons with different alleles for a particular gene are said to be heterozygous,
those with identical alleles on both chromosomes are homozygous. The genome is
the sum total of all genes and connecting sequences present in an individual or a
population. The term ‘genome’ can be used to refer to one unique series of genes
(haploid genome), to the redundant series of genes present in an organism (diploid
genome), or to the collection of genes present in a large number of individuals under
study (population or species genome). Such distinctions are important, because it is
often assumed that information from population studies may be directly applied back
to individuals. This may or may not be the case, as will be discussed later.
DNA is made up of a combination of four chemical bases, referred to by the letters
A, C, G and T. A string of such letters makes up a DNA sequence, such as AATGCG.
By default, the most common combination of letters found in a particular region of
the genome is taken to be the ‘normal’ sequence. Differences from that order of nucle-
otides are considered to be DNA variants. Many variants are possible. In the example
above, the sequence AAGGCG would be considered a variant, because it differs at the
third position from the left: a G exists where a T would normally be found. Variants
that change one chemical letter are referred to as point mutations or single nucleotide
polymorphisms (SNPs), depending on their frequency in the population and whether
they have a major effect on health. If the AATGCG sequence were present in 55%
of the sequences in a study population, and the AAGGCG sequence were present
in 45%, the ‘T’ variant would be considered the ‘normal variant,’ and the ‘G’ variant
would be considered a SNP. If, on the other hand, 99.95% of sequences studied were
found to be AATGCG and 0.05% were found to be AAGGCG, the ‘G’ would be con-
sidered a rare variant and termed a ‘mutation’. Debate exists whether the term ‘muta-
tion’ should be reserved exclusively for when the ‘mutant’ DNA sequence has major
effects on physical characteristics, or perhaps for when the variant can be proven to
have arisen at a definable time. For rare disorders wherein a DNA sequence variant
is 100% associated with disease, the use of ‘mutation’ is well-recognized. In human
population studies wherein the function of the DNA sequence may not be clear, the
2 Gibson