Genetics Primer for Exercise Science and Health

193 Pages·2007·6.09 MB·English

by  Stephen M. Roth

Primers in Exercise Science Series
Genetics Primer
for Exercise
Science and Health

Stephen M. Roth, PhD
University of Maryland
Note: This e-book reproduces the text of the printed book, but it may not include images, tables, or
figures that have restrictions on electronic distribution.
Human Kinetics
Library of Congress Cataloging-in-Publication Data
Roth, Stephen M., 1973-
Genetics primer for exercise science and health / Stephen M. Roth.
p. ; cm. -- (Primers for exercise science series)
Includes bibliographical references and index.
ISBN-13: 978-0-7360-6343-2 (soft cover)
ISBN-10: 0-7360-6343-9 (soft cover)
1. Human genetics. 2. Exercise--Physiological aspects. 3. Sports--Physiological aspects. I. Title. II. Series.
[DNLM: 1. Genetics. 2. Physical Fitness--physiology. 3. Exercise--physiology. 4. Genetic Techniques. 5. Variation (Genetics) QU
500 R845g 2007]
QH431.R84 2007
612’.044--dc22
2007004421
ISBN-10: 0-7360-6343-9 (print) ISBN-10: 0-7360-9072-X (Adobe PDF)
ISBN-13: 978-0-7360-6343-2 (print) ISBN-13: 978-0-7360-9072-8 (Adobe PDF)
Copyright © 2007 by Stephen M. Roth
All rights reserved. Except for use in a review, the reproduction or utilization of this work in any form or by any electronic,
mechanical, or other means, now known or hereafter invented, including xerography, photocopying, and recording, and in any
information storage and retrieval system, is forbidden without the written permission of the publisher.
The Web addresses cited in this text were current as of March 15, 2007, unless otherwise noted.
Acquisitions Editor: Michael S. Bahrke, PhD; Developmental Editor: Christine M. Drews; Assistant Editor: Maureen
Eckstein and Laura Koritz; Copyeditor: Joyce Sexton; Proofreader: Sarah Wiseman; Indexer: Craig Brown; Permissions
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Fitch; Photo Office Assistant: Jason Allen; Cover Designer: Robert Reuther; Art Manager: Kelly Hendren; Illustrator:
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Human Kinetics
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United States: Human Kinetics, P.O. Box 5076, Champaign, IL 61825-5076
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[phone]
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New Zealand: Human Kinetics, Division of Sports Distributors NZ Ltd., P.O. Box 300 226 Albany, North Shore City, Auckland
0064 9 448 1207
e-mail: [email protected]
To my wife, Nancy, and our children, Nels, Ellyn, and Anna

Contents
Preface xi
Acknowledgments xiii
I
Part Basics of Genetics . . . . . . . . . . . . . . . . . 1
1
Individual Differences: The Role of
CHaPtEr
Genetics in Exercise Science and Health . . . . . 3
Hidden Aspect of Average Values . . . . . . . . . . . . . . . . . . . . . . . 3
Why Do We See Variation in a Physical Trait? . . . . . . . . . . . . . . 6
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
2
DNA, RNA, and Protein . . . . . . . . . . . . . . . . . . . 9
CHaPtEr
Basic Cell Biology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9
DNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .10
Our Genetic Material as Chromosomes . . . . . . . . . . . . . . . . . . .11
Special Focus: The Human Genome Project . . . . . . . . . . . . . . 12
RNA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .13
Amino Acids and Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . .14
Structure of Genes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .15
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .17
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .18
3
Transcription, Translation,
CHaPtEr
and the Genetic Code . . . . . . . . . . . . . . . . . . . 19
Moving from DNA to RNA: Transcription . . . . . . . . . . . . . . . . .19
Posttranscriptional Modifications of RNA . . . . . . . . . . . . . . . . 20
Moving from RNA to Protein: Translation . . . . . . . . . . . . . . . . .21
Posttranslational Modifications of Proteins . . . . . . . . . . . . . . . 22
Genetic Code . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 23
v
vi CONTENTS
4
Moving Genetic Material
CHaPtEr
to the Next Generation . . . . . . . . . . . . . . . . . . 25
Basic Reproduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25
Sex Cell Production and Meiosis . . . . . . . . . . . . . . . . . . . . . . . 26
Special Focus: Mitosis Versus Meiosis . . . . . . . . . . . . . . . . . . . 26
Chromosomal Recombination . . . . . . . . . . . . . . . . . . . . . . . . . 28
Mendelian Inheritance Patterns . . . . . . . . . . . . . . . . . . . . . . . . 30
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
5
Heritability and the Basics
CHaPtEr
of Genetic Variation . . . . . . . . . . . . . . . . . . . . 35
Familial Resemblance: Genes and Environment . . . . . . . . . . . .35
Heritability as a Measure of Genetic Contribution . . . . . . . . . 36
Genetic Variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Special Focus: Twin and Family Studies . . . . . . . . . . . . . . . . . 39
Types of Genetic Variation . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Special Focus: Labeling Polymorphisms . . . . . . . . . . . . . . . . . 42
How Genetic Variation Can Influence Physical Traits . . . . . . . 44
How Do Polymorphisms Arise?
Genetic Variation and Evolution . . . . . . . . . . . . . . . . . . . . . . .47
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 48
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49
6
Genetic Variation and Disease . . . . . . . . . . . . 51
CHaPtEr
Mendelian Disease Genetics . . . . . . . . . . . . . . . . . . . . . . . . . . . .51
Special Focus: Muscular Dystrophy . . . . . . . . . . . . . . . . . . . . 53
Complex Disease . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 54
Gene 3 Environment Interactions . . . . . . . . . . . . . . . . . . . . . . 56
Special Focus: Obesity as a Complex Trait . . . . . . . . . . . . . . . .57
Gene 3 Gene Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 58
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 59
CONTENTS vii
7
Linkage Disequilibrium, Haplotype,
CHaPtEr
and Environmental Interaction. . . . . . . . . . . . 61
Recombination Revisited . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .61
Linkage Disequilibrium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
Linkage Analysis in Families . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Haplotype: Combinations of Neighboring Alleles . . . . . . . . . . 67
Special Focus: The International HapMap Project . . . . . . . . . 69
Diplotype: Combinations of Haplotypes . . . . . . . . . . . . . . . . . 70
Gene 3 Environment Interaction Revisited . . . . . . . . . . . . . . . 72
An Introduction to Epigenetics . . . . . . . . . . . . . . . . . . . . . . . . . 72
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .74
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .74
II
Part Research Design and Methods . . .75
8
Getting Started:
CHaPtEr
Basic Skills for Genetics Research . . . . . . . . . 77
Is Genetic Variation Important for My Trait of Interest? . . . . . 77
Using PubMed . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 79
Interpreting Existing Literature . . . . . . . . . . . . . . . . . . . . . . . . 79
Identifying and Selecting Candidate Genes
and Polymorphisms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Using Genome Databases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 82
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84
9
Issues in Study Design and Analysis . . . . . . . 85
CHaPtEr
How Genetics Necessarily Alters Study Design . . . . . . . . . . . . 85
Typical Study Designs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 87
Subject Recruitment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Geographic Ancestry . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90
Special Focus: Race in Genetics . . . . . . . . . . . . . . . . . . . . . . . 92
Prospective Versus Retrospective . . . . . . . . . . . . . . . . . . . . . . 93
Statistical Approaches . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 94
Interpretation of Results:
Association Versus Cause and Effect . . . . . . . . . . . . . . . . . . 95
viii CONTENTS
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96
10
Basic Laboratory Methods in Genetics . . . . . . 99
CHaPtEr
DNA From Blood or Cheek Cells . . . . . . . . . . . . . . . . . . . . . . . . 99
Polymerase Chain Reaction (PCR) . . . . . . . . . . . . . . . . . . . . . .100
Genotyping With Restriction Enzymes . . . . . . . . . . . . . . . . . .103
Genotyping With Fluorescent Tags . . . . . . . . . . . . . . . . . . . . .105
DNA Sequencing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .106
Special Focus: DNA Microarrays . . . . . . . . . . . . . . . . . . . . . .107
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .110
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .110
III
Part Current Findings and Extensions
of Genetics Research 111
. . . . . . . . . . .
11
Current Research Findings in the
CHaPtEr
Genetics of Exercise Science and Health . . . 113
Overview of Current Findings . . . . . . . . . . . . . . . . . . . . . . . . .113
Special Focus: The Human Gene Map for Performance
and Health-Related Fitness Phenotypes . . . . . . . . . . . . . . . . .114
ACTN3 and Muscle Performance . . . . . . . . . . . . . . . . . . . . . . .116
ApoE and Cognitive Impairment . . . . . . . . . . . . . . . . . . . . . . .118
ACE and Sport Performance . . . . . . . . . . . . . . . . . . . . . . . . . . .121
Myostatin and Muscle Mass . . . . . . . . . . . . . . . . . . . . . . . . . . .124
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .127
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .128
12
Personalized Medicine . . . . . . . . . . . . . . . . . 129
CHaPtEr
Genetics and Complex Disease Revisited . . . . . . . . . . . . . . . .129
Promise and Limitations of Personalized Medicine . . . . . . . .130
Special Focus: Pharmacogenomics . . . . . . . . . . . . . . . . . . . .131
Genetics in Nutrition and Exercise Prescription . . . . . . . . . . .132
Genetics in Disease Prevention . . . . . . . . . . . . . . . . . . . . . . . 134
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .135
Learning Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .135
CONTENTS ix
13
Ethical Challenges in Genetics and Society . . 137
CHaPtEr
Ethical, Legal, and Social Implications of Genomics . . . . . . . .137
Gene Therapy for Disease Treatment . . . . . . . . . . . . . . . . . . .140
Special Focus: Stem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . .142
Genetics in Sport: Genetic Testing and Gene Doping
for Performance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .143
Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .145
Learnings Aids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .145
Appendix A Answers to Review Questions 147
Appendix B Evolution and Hardy-Weinberg Equilibrium 153
Glossary 157
Bibliography 165
Index 169
About the Author 177