Essentials of Genomic and Personalized Medicine

851 Pages·2009·1.59 MB·English

by  Geoffrey S. Ginsburg, Huntington Ph.D Willard

E ssentials of Genomic and
Personalized Medicine
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E ssentials of Genomic and
Personalized Medicine
E dited by
Geoffrey S. Ginsburg, M.D., Ph.D.
Center Director, Center for Genomic Medicine
Duke Institute for Genome Sciences & Policy
Professor of Medicine
Duke University Medical Center
Durham, North Carolina 27708
and
Huntington F. Willard, Ph.D.
Director
Duke Institute for Genome Sciences & Policy
Nanaline H. Duke Professor of Genome Sciences
Howard Hughes Medical Institute Professor
Duke University
Durham, North Carolina 27708
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F irst edition 2010
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Table of Contents
Preface ix 9 Comprehensive Metabolic Analysis for Understanding
of Disease 97
Abreviations xi
Christopher B. Newgard, Robert D. Stevens, Brett R. Wenner,
Contributors xix Shawn C. Burgess, Olga Ilkayeva, Michael J. Muehlbauer,
A. Dean Sherry and James R. Bain
1 The Foundations of Genomic and Personalized
Medicine 1
Geofrey S. Ginsburg and Huntington F. W ilard SECTION 2 INFORMATICS
10 Bioinformatic and Computational Analysis for
Genomic Medicine 111
Atul J. Butte
SECTION 1 BASICS
2 Organization, Variation and Expression of 11 Systems Biology and Systems Medicine 131
the Human Genome 13 Nathan D. Price, Lucas B. Edelman, Inyoul Lee, Hyuntae Yoo,
Huntington F. Willard Daehee Hwang, George Carlson, David J. Galas, James R.
Heath and Leroy Hood
3 DNA Sequencing for the Detection of Human 12 Electronic Medical Records in Genomic Medicine
Genome Variation 27 Practice and Research 142
Samuel Levy and Yu-Hui Rogers Glenn S. Gerhard, Robert D. Langer, David J. Carey and
Walter F. Stewart
4 Genome-Wide Association Studies and Genotyping
Technologies 38 13 Online Health Information Retrieval by Consumers 151
Kevin V. Shianna Mark S. Boguski
5 Copy Number Variation and Human Health 46
Charles Lee, Courtney Hyland, Arthur S. Lee, Shona Hislop
and Chunhwa Ihm SECTION 3 TRANSLATIONAL
14 Translational Genomics: From Discovery to Clinical
6 DNA Methylation Analysis: Providing New Insight Practice 163
into Human Disease 60 Geoffrey S. Ginsburg
Susan Cottrell, Theo deVos, Juergen Distler, Carolina Haefl iger,
Ralf Lesche, Achim Plum and Matthias Schuster 15 Pharmacogenetics and Pharmacogenomics 175
Iris Grossman and David B. Goldstein
7 DNA Microarrays in Biological Discovery and 16
Clinical Implementation of Translational
Patient Care 73 Genomics 191
Andrew J. Yee and Sridhar Ramaswamy Wendy K. Chung
8 Proteomics: The Deciphering of the Functional 17 The Role of Genomics in Enabling Prospective
Genome 89 Health Care 201
Li-Rong Yu, Nicolas A. Stewart and Timothy D. Veenstra Ralph Snyderman
v
vi ■ Table of Contents
18 Genome Policy Considerations for Genomic
Medicine 209 SECTION 5 CLINICAL (ONCOLOGY)
Susanne B. Haga
32 Genomics in the Management of Lymphomas 407
Lisa Rimsza
19 Federal Regulation of Genomic Medicine 223
Janet Woodcock
33 Genomics in Leukemias 421
Lars Bullinger, Hartmut Dohner and Jonathan R. Pollack
20 Economic Issues and Genomic Medicine 233
David L. Veenstra, Louis P. Garrison and Scott D. Ramsey
34 Genomics in the Diagnosis and Management
of Lung Cancer 432
21 Public Health Genomics 245 Hasmeena Kathuria, Avrum Spira and Jerome Brody
Alison Stewart, Marta Gwinn, Ron Zimmern and
Muin Khoury 35 Genomics in the Diagnosis and Management of
Breast Cancer 446
Erich S. Huang and Andrew T. Huang
SECTION 4 CLINICAL (CARDIOLOGY) 36 Colorectal Cancer 457
G.L. Wiesner, T.P. Slavin and J.S. Barnholtz-Sloan
22 The Genomics of Hypertension 259
Chana Yagil and Yoram Yagil
37 Genomic Evaluation and Management of Prostate
Cancer 47
23 Lipoprotein Disorders 269 Phillip G. Febbo and Philip W. Kantoff
Sekar Kathiresan and Daniel J. Rader
38 Genomic Assessment of Ovarian Cancer 493
24 Genomics of Myocardial Infarction 289 Tanja Pejovic, Matthew L. Anderson and Kunle Odunsi
Carlos A. Hubbard and Eric J. Topol
39 Genomic Evaluation of Pancreatic Neoplasms 501
25 Acute Coronary Syndromes 303 Asif Khalid and Kevin McGrath
L. Kristin Newby
40 Genomic Evaluation of Head and Neck Cancer 511
Giovana R. Thomas and Yelizaveta Shnayder
26 Heart Failure in the Era of Genomic Medicine 313
Ivor J. Benjamin and Jeetendra Patel
41 Genomic Evaluation of Brain Tumors and Gliomas 522
Sean E. Lawler and E. Antonio Chiocca
27 Genomic Assessment of Cardiac Transplant
Rejection 326
42 Targeted Therapies for Cancer 532
Michael Pham, Mario C. Deng, Jay Wohlgemuth and
Jeffrey S. Ross
Thomas Quertermous
28 Genetics and Genomics of Hypertrophic
Cardiomyopathy 336
J. Martijn Bos, Steve R. Ommen and Michael J. Ackerman SECTION 6 C LINICAL
(INFLAMMATORY DISEASE)
29 Genetics and Genomics of Arrhythmias 350
43 Genomics in the Evaluation and Management of
Jeffrey A. Towbin and Matteo Vatta
Rheumatoid Arthritis 551
Robert M. Plenge and Michael E. Weinblatt
30 Genetics and Genomics in the Management of
Hemostasis and Thrombosis 374 44 Genomic Evaluation of Multiple Sclerosis 566
Richard C. Becker and Felicita Andreotti Francisco J. Quintana and Howard L. Weiner
31 Genomics of Congenital Heart Disease 390 45 Genomic Assessment of Infl ammatory Bowel Disease 575
Jessie H. Conta and Roger E. Breitbart Ad A. van Bodegraven and Cisca Wijmenga
Table of Contents ■ vii
46 Asthma Genomics 590 54 Genetics and Genomics of Parkinson’s Disease 700
Scott T. Weiss, Benjamin A. Raby and Juan C. Celedón Shushant Jain and Andrew B. Singleton
47 Genomics in the Evaluation and Management of 55 Genomic Considerations in Ophthalmology 712
Chronic Obstructive Pulmonary Disease 603 Janey L. Wiggs
Peter J. Barnes
56 Genomics in the Diagnosis and Management of
48 Genetics and Genomics of Interstitial Lung Disease 616 Depresion 722
Paul W. Noble and Mark P. Steele Brigitta Bondy
49 Peptic Ulcer Disease 627
John Holton
SECTION 9 C LINICAL (INFECTIOUS
DISEASE)
57 Genomic Approaches to the Host Response to
SECTION 7 C LINICAL (METABOLIC Pathogens 733
M. Frances Shannon
DISEASE)
50 Genomics in Pathogenesis of Cirrhosis 645
58 Host Genomics and Bacterial Infections 744
N.A. Shackel, K. Patel and J. McHutchison
Melissa D. Johnson and Mihai Netea
51 Genomic Medicine and Obesity 661
59 Genomics in the Evaluation and Management
J. Alfredo Martínez
of Sepsis 760
Christopher W. Woods, Robert J. Feezor and
52 Diabetes 676 Stephen F. Kingsmore
Maggie Ng and Nancy J. Cox
60 Genomics and the Management of Hepatitis 774
N.A. Shackel, K. Patel and J. McHutchison
SECTION 8 C LINICAL
Index 787
(NEUROLOGICAL
DISEASE)
53 Genetics and Genomics of Dementia 687
Robert L. Nussbaum
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Preface
With the completion of the Human Genome Project at the ● target medicines and their dose more precisely and safely to
beginning of this decade and the rapid development and appli- each patient, on the basis of a deep understanding of disease
cation of new advances in our ability to understand and query mechanism and the role that genetic and genomic factors
the human genome and its gene set, it is time already to review play in the individual response to drugs.
the early sketches of a much-anticipated transformation of the
The time for this revolution in genomic and personalized
practice of medicine. We have seen the very fi rst signs of a funda-
medicine has come. As its name suggests, this book is intended
mental shift in how we behold human physiology and pathology,
to lay out the essentials of this new approach to medicine and to
how we view the concept of what is “normal”, how we con-
emphasize for particular conditions the clinical opportunities that
sider individuals and their prospects for lifelong health, and how
present themselves today. It is designed to complement the more
we design health care systems that are equally adaptable to the
comprehensive two-volume book Genomic and Personalized Medicine,
demands of population-wide epidemics and the opportunities for
published last year, which presented in substantial depth the foun-
personalized care that utilizes genome-based information to con-
dations of this new science, outlined the early opportunities for the
sider individual susceptibility to disease and therapeutic options.
practice of medicine to incorporate genome-based analysis into
Genome-based data, information, knowledge, and eventually
health care, and anticipated the many conditions to which genomic
wisdom will make possible the kind of health care that has been
and personalized medicine will apply in the years ahead.
dreamed of since the advent of disease-based medicine early in
This volume on Essentials of Genomic and Personalized
the 20th century. A system of health care that harnesses the data
Medicine describes an emerging fi eld that spans the breadth of
intensity of the genome and its derivatives, along with imaging,
clinical medicine, with many challenges for society at large and
clinical, and environmental information, will empower physi-
for health care systems in particular. Nonetheless, we are opti-
cians and other health care providers to do what they have always
mistic that the appropriate delivery models and economic incen-
aspired to do – make medical care as individualized as possible.
tives will be developed in a trustworthy framework that will be
But this newfound information and knowledge will also allow
embraced by societies around the globe.
each of us as consumers of health care to take more control
Our intended audience is clinically oriented but broad,
of our futures and to develop a more strategic and prospective
ranging from medical students to residents and fellows to prac-
approach to health. We stand at the dawn of a profound change in
titioners in any of the health care professions – physicians in any
science and medicine’s predictive nature and in our understand-
of the medical specialties, surgeons, nurses, genetic (and genomic)
ing of the biological underpinnings of health and disease. Even in
counselors, and laboratory directors.
this early light, we can see the outlines of a coming ability to:
In times of transformation, we are all students. We hope that
● predict individual susceptibility to disease, based on genetic, this Essentials volume will help usher in this new era of genomic
genomic, and other factors; and personalized medicine and will provide a useful and thor-
● provide more useful tools and individualized programs for dis- ough introduction to the science and practice of this new
ease prevention, based on knowledge of one’s susceptibility; approach to human health.
● detect the onset of disease earlier and before it is clinically
evident, based on newly discovered biological markers that Geoffrey S. Ginsburg, M.D., Ph.D.
arise from changes at the molecular level; Huntington F. Willard, Ph.D.
● preempt disease progression, as a result of early detection; and June 2009
ix