GENOMICS AND PERSONALIZED MEDICINE WHAT EVERYONE NEEDS TO KNOW® GENOMICS AND PERSONALIZED MEDICINE WHAT EVERYONE NEEDS TO KNOW® MICHAEL SNYDER 1 3 Oxford University Press is a department of the University of Oxford. It furthers the University’s objective of excellence in research, scholarship, and education by publishing worldwide.Oxford is a registered trade mark of Oxford University Press in the UK and certain other countries. “What Everyone Needs to Know” is a registered trademark of Oxford University Press. Published in the United States of America by Oxford University Press 198 Madison Avenue, New York, NY 10016, United States of America. © Oxford University Press 2016 First Edition published in 2016 All rights reserved. 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Library of Congress Cataloging- in- Publication Data CIP data on file with Library of Congress ISBN 978–0–19–023476-8 1 3 5 7 9 8 6 4 2 Printed by Sheridan, USA CONTENTS ACKNOWLEDGMENTS  XI INTRODUCTION  XIII 1 Personalized Medicine  1 What is personalized medicine?  1 What personal factors impact our health?  2 2 Genome Fundamentals  5 What is DNA?  5 What is a genome?  7 What does the genome do?  9 How does one person’s genome differ from another person’s genome?  9 How do genomes of men and women differ?  12 How is the genome decoded?  13 3 An Introduction to Cancer Genetics  21 What is cancer and how does it arise?  21 How do the BRCA1 and BRCA2 genes cause cancer?  24 vi CONTENTS What are examples of other genes implicated in cancer?  25 How does genetic information help us treat cancer?  26 4 Genomics and Cancer Treatment  31 What has been learned from genome sequencing of cancer?  31 How can genome sequencing advance cancer treatment?  32 If I have cancer should I get my tumor genome sequenced?  37 Why do anticancer drugs fail and how might genomic approaches help address this issue?  39 Can genetics and genomics help detect early cancer and monitor treatment effectiveness?  41 A new approach: What is immunotherapy?  42 How can genomics be used to harness the patient’s own immune system to fight cancer?  44 5 Solving Mystery Diseases  47 What is a mystery genetic disease?  47 How many Mendelian diseases are there?  49 How are genes responsible for genetic disorders identified?  50 How useful are genomic approaches to solving mystery genetic diseases?  53 Why can’t most Mendelian diseases be solved?  55 6 Complex Genetic Diseases  59 What is a complex genetic disease?  59 How does complex genetics affect neurological diseases?  61 How does complex genetics affect metabolic diseases?  62 Can some diseases be both monogenic and complex?  64 Contents vii 7 Pharmacogenomics  67 How can your genome directly help guide drug treatments for treating disease?  67 What are other ways your DNA can guide drug treatments?  67 Are there sex differences in drug effects?  69 8 Genomics for the Healthy Person  71 How can getting your genome sequenced improve your health?  71 Can genome sequencing affect the drugs someone takes?  76 Can genetic testing be used to predict sports performance and injuries?  78 Will sequencing my genome affect my children and my relatives?  79 9 Prenatal Testing  81 How are genome sequencing technologies changing prenatal testing?  81 Can genome sequencing be used to identify other mutations, beyond chromosomal abnormalities, that might cause disease?  83 Can genetic testing be useful for choosing healthier embryos and producing designer babies?  84 10 Effects of the Environment on the Genome and Epigenetics  87 How does the environment contribute to health?  87 When did people first begin to study environmental effects?  87 When do environmental effects begin?  88 Can environmental factors directly impact the genome?  89 What is epigenetics?  89 What are some examples of environmental effects on physiology that are mediated through epigenetics?  91 viii CONTENTS What is the role of epigenetics in disease?  92 How will increased understanding of epigenetics impact health care?  92 11 Other ‘Omes  95 What other ‘omes are useful for medicine?  95 How can the transcriptome and proteome be useful?  96 How can the metabolome be useful?  97 How deeply can a person be analyzed?  99 12 The Personal Microbiome  101 What is the microbiome?  101 How is the microbiome studied?  102 How does the microbiome affect health?  104 How does diet affect the microbiome?  106 Can the microbiome affect other aspects of our lives?  106 Can the microbiome be altered to improve human health?  107 13 Your Immune System and Infectious Diseases  109 How does your immune system protect you?  109 How does the immune system vary among people and affect our health?  111 How can we analyze infectious diseases?  112 14 Aging and Health  115 Are there genetic factors underlying longevity?  115 Are there environmental factors that affect aging and longevity?  117 Does epigenetics control aging?  118 Will we someday be able to control our aging?  119 Contents ix 15 Wearable Health Devices  121 What other types of personal health information can be readily collected?  121 How will this information be made available to, and used by, the individual?  124 16 Big Data and Medicine  125 How much data can be gathered about a single person?  125 How much data can be gathered about a group of people?  126 How can a large database assist in medical care?  127 How can Big Data guide lifestyle decisions?  130 What are the opportunities for industry in Big Data Medicine?  130 17 Delivery of Genomic Information  133 Who controls your genomic and other health information?  133 Who will deliver genomic information to you?  134 What is the role of the physician?  135 What are the implications of direct- to- consumer genomic testing?  136 18 Ethics  139 Can your genetic information be used against you?  139 What are the concerns surrounding routine (or even mandated) genetic screening?  140 What is a possible solution?  141 19 Education  143 Can we educate people to understand genomic information?  143 How do we educate physicians to understand genomic information?  144