Routledge Handbook of Sport and Exercise Systems Genetics

J. Timothy Lightfoot, Monica Hubal, Stephen Roth, J. Timothy Lightfoot, Monica J. Hubal, Stephen M. Roth

• Publisher: Routledge
• Year: 2019
• ISBN:
  9781351380157
• Edition: 1
• Topic: Medicina
• Subtopic: Fisiologia

Technological advances over the last two decades have placed genetic research at the forefront of sport and exercise science. It provides potential answers to some of contemporary sport and exercise's defining issues and throws up some of the area's most challenging ethical questions, but to date, it has rested on a fragmented and disparate literature base. The Routledge Handbook of Sport and Exercise Systems Genetics constitutes the most authoritative and comprehensive reference in this critical area of study, consolidating knowledge and providing a framework for interpreting future research findings.

Taking an approach which covers single gene variations, through genomics, epigenetics, and proteomics, to environmental and dietary influences on genetic mechanisms, the book is divided into seven sections. It examines state-of-the-art genetic methods, applies its approach to physical activity, exercise endurance, muscle strength, and sports performance, and discusses the ethical considerations associated with genetic research in sport and exercise.

Made up of contributions from some of the world's leading sport and exercise scientists and including chapters on important topical issues such as gene doping, gender testing, predicting sport performance and injury risk, and using genetic information to inform physical activity and health debates, the handbook is a vital addition to the sport and exercise literature. It is an important reference for any upper-level student, researcher, or practitioner working in the genetics of sport and exercise or exercise physiology, and crucial reading for any social scientist interested in the ethics of sport.

SECTION 1

General systems genetics

Introduction

With the completion of the first human genome sequence in 2000, scientific and public interest increased in regard to the impact of genetics on a wide variety of physiological traits. Sport and exercise traits were no exception, with many in the public and in science questioning the role that “genetics” played in both sport and exercise performance. However, because most sport and exercise scientists had/have little in the way of genetics background and training, catching up and keeping up with the rapid changes occurring in genetics continues to be a major challenge for the application of genetics to sport and exercise questions. Thus, the following four chapters aim to provide a foundation for the systems genetics concepts and techniques that are described and discussed in the remainder of the book.

As it should be with a general foundational section, the set of chapters that make up this section is wide ranging with each written by an acknowledged international leader in the field. The first chapter, written by Dr. Frank Booth and co-workers, encompasses a broad overview of why considering systems genetics is important, with the consistent context of the chapter focused on the personal and health cost of physical inactivity.

Maybe more than any other scientific discipline, the conceptual and theoretical framework of genetics has undergone massive changes in the past 20 years. Much of the genetics many of us learned before 2000 is obsolete and so the second chapter, by Dr. Penny Riggs, is a review of the major changes in genetics since the sequencing of the human genome, with an emphasis on the new concepts such as miRNA and epigenetics that can and should be applied to exercise and sport.

Physiologists do not often consider how the individual’s genetic makeup could alter the responses that are observed during experiments, when in fact the genetic framework of an individual (or animal) can lead to marked differences during an experiment. Therefore, appropriate modeling systems are critical in genetic studies, so Chapter 3 provides an overview of the common human modeling systems used in genetic studies by Dr. Jaakko Kaprio.

Lastly, understanding the mechanisms and modeling are important, but most scientists agree that if we cannot apply the results to a population in general, then our science has difficulty making a difference. That is why the section finishes with a critical chapter by Dr. Molly Bray dedicated to how we can apply systems genetics to translational models and everyday life, with Dr. Bray using physical activity as the exercise phenotype described.

We believe that these four chapters will provide a great foundation for the rest of the book. You will find that the basic concepts covered in these chapters will be returned to repeatedly throughout the rest of the book as specific exercise and sport situations are dealt with. Due to the foundational nature of these chapters, we are grateful that these scientific thought leaders all agreed to participate. Enjoy!

1

WHY STUDY THE SYSTEMS GENETICS OF SPORT AND EXERCISE?

Frank W. Booth, Taylor J. Kelty, Kolter B. Grigsby, and Gregory N. Ruegsegger

Introduction

This chapter is tilted toward the authors’ perspective of the future of exercise science in contrast to our recent reviews (8, 9, 44) which were more focused on the retrospective side of exercise mechanisms. Both types of reviews can be controversial. However, perspective reviews distinguish themselves in that they are based more upon an opinion of the future, and less on data from the literature. As such, the future being unpredictable, the authors’ comments could be considered to provide backgrounds for future research considerations as well as the rest of the chapters of this volume.

Exercise systems genomics

This section bookends the final contributed chapter of the book, which is written by the founder of the field of exercise genomics, Claude Bouchard. Bouchard’s tremendous foresights allowed him to establish exercise systems genetics in humans three decades before systems genetics was recognized as a field. Bouchard began phenotyping exercise as early as 1976 (14), when he correlated variables with skeletal maturity and chronological age in 8–18-year-old boys. A 1980 paper (12) was about estimates of sibling correlations and genetic/heritability estimates in a number of French-Canadian families which was extended in 1983 by an overall review of the genetics of physiological fitness (13). Furthermore, Bouchard pioneered the integration of exercise training and genetics in his classical Heritage family study (10, 11). In 2007, the term “systems genomics” began being popularized (35) to include Bouchard’s older science of “exercise genomics.” In 1999, he already had performed sufficient studies to conclude that trainability of VO₂max had a significant genetic component based upon considerable heterogeneity in degree of increase in VO₂max following the same endurance-training program in 481 sedentary, adult Caucasians from 98 two-generation families. With the establishment of exercise genomics and exercise systems genomics, a wide variety of exercise characteristics can be viewed through the lens of exercise systems genetics.

One example of exercise systems genetics is that contracting skeletal muscle releases peptides (termed myokines (22, 39)) into capillaries. The myokines then circulate to a distant site (i.e., cells, tissues, or organs) where they initiate a cascade to have a subsequent biochemical effect at that site (25, 37). The first investigator to identify a molecule that fitted the criteria to have an endocrine-like function from skeletal muscle was Pedersen, whose lab reported in 1994 that blood interleukin (IL)-6 increased during exercise (52). Then, in 2003, Pedersen proposed, “IL-6 and other cytokines, which are produced and released by skeletal muscles, exerting their effects in other organs of the body, should be named ‘myokines’” (38). IL-6 is now the prototype myokine emulating skeletal muscle-to-organ crosstalk, or systems genetics. Recently, Whitham et al. (54) reported that many circulating proteins are packaged within extracellular vesicles that also perform tissue crosstalk during exercise to produce systemic biological effects. Our notion is that components in the extracellular vesicles could form another candidate for the therapeutic manipulation of some of the thousands of positive molecular benefits of exercise.

The challenge of understanding the above example was reflected in a 2017 opinion piece where 16 invited experts presented their viewpoints on the status and future of systems genetics (5). The experts’ consensus opinion was: “deciphering genotype to phenotype relationships is a central challenge of systems genetics and will require understanding how networks and higher-order properties of biological systems underlie complex traits” (5). The authors’ interpretation of systems genetics in relationship to physical activity and physical inactivity will be considered in the next section.

Exercise presents a high stress; however, the body is able to survive by maintaining its homeostasis during performance

Exercise is stress. Stress has numerous definitions. The operational definition for stress used herein is an increased blood cortisol concentration. As such, maximal exercise effort is one of the greatest stressors to the body. An underlying reason for intense exercise, and thus intense stress, was postulated by Charles Darwin. On a statistical basis, those who are physically unfit are more likely to be eliminated prior to their being able to reach reproductive age. Herbert Spencer coined the phrase “survival of the fittest.” It is unlikely that the pre-adolescent individual of 5000 years ago, who never had the capability to perform physical activity, could have survived to puberty to perpetuate their genes to the next generation. Thus, their gene pool would be extinguished and not passed on to the next generation (21). Today, the elimination of infectious diseases allows most individuals in developed communities to live t...