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Essentials of Genomic and
Personalized Medicine
This page intentionally left blank
Essentials of Genomic and
Personalized Medicine
Edited 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

AMSTERDAM • BOSTON • HEIDELBERG • LONDON • NEW YORK • OXFORD • PARIS

SAN DIEGO • SAN FRANCISCO • SYDNEY • TOKYO
Academic Press is an imprint of Elsevier
Academic Press is an imprint of Elsevier
525 B Street, Suite 1900, San Diego, CA 92101-4495, USA
30 Corporate Drive, Suite 400, Burlington, MA 01803, USA
32 Jamestown Road, London NW1 7BY, UK

First edition 2010

Copyright © 2010 Elsevier Inc, except Chapter 54 which is in the public domain. All rights reserved

No part of this publication may be reproduced, stored in a retrieval system

or transmitted in any form or by any means electronic, mechanical, photocopying,
recording or otherwise without the prior written permission of the publisher

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Department in Oxford, UK: phone (44) (0) 1865 843830; fax (44) (0) 1865 853333;
email: [email protected]. Alternatively visit the Science and Technology Books
website at www.elsevierdirect.com/rights for further information

Notice
No responsibility is assumed by the publisher for any injury and/or damage to persons
or property as a matter of products liability, negligence or otherwise, or from any use
or operation of any methods, products, instructions or ideas contained in the material
herein. Because of rapid advances in the medical sciences, in particular, independent
verification of diagnoses and drug dosages should be made

British Library Cataloguing-in-Publication Data

A catalogue record for this book is available from the British Library

Library of Congress Cataloging-in-Publication Data

A catalog record for this book is available from the Library of Congress

ISBN: 978-0-12-374934-5

For information on all Academic Press publications

visit our website at www.books.elsevier.com

Typeset by Macmillan Publishing Solutions

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Printed and bound in Canada

10 11 12 13 14 15 10 9 8 7 6 5 4 3 2 1
 Table of Contents
Preface ix 9 Comprehensive Metabolic Analysis for Understanding
of Disease 97
Abbreviations 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
Geoffrey S. Ginsburg and Huntington F. Willard SECTION 2 INFORMATICS
10 Bioinformatic and Computational Analysis for
Genomic Medicine 111
Atul J. Butte
SECTION 1 BASICS
11 Systems Biology and Systems Medicine 131
2 Organization,Variation and Expression of
Nathan D. Price, Lucas B. Edelman, Inyoul Lee, Hyuntae Yoo,
the Human Genome 13
Daehee Hwang, George Carlson, David J. Galas, James R.
Huntington F. Willard
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 Haefliger,
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 477
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
26 Heart Failure in the Era of Genomic Medicine 313 Giovana R.Thomas and Yelizaveta Shnayder
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
Michael Pham, Mario C. Deng, Jay Wohlgemuth and 42 Targeted Therapies for Cancer 532
Thomas Quertermous Jeffrey S. Ross

28 Genetics and Genomics of Hypertrophic

Cardiomyopathy 336
J. Martijn Bos, Steve R. Ommen and Michael J. Ackerman SECTION 6 CLINICAL
(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 Inflammatory 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 Depression 722
Paul W. Noble and Mark P. Steele Brigitta Bondy

49 Peptic Ulcer Disease 627

John Holton
SECTION 9 CLINICAL (INFECTIOUS
DISEASE)
57 Genomic Approaches to the Host Response to
SECTION 7 CLINICAL (METABOLIC Pathogens 733
DISEASE) M. Frances Shannon

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 CLINICAL Index 787

(NEUROLOGICAL
DISEASE)
53 Genetics and Genomics of Dementia 687
Robert L. Nussbaum
This page intentionally left blank
 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 first 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 field 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
This page intentionally left blank
 Abbreviations

2D-DIGE Two-dimensional difference gel electrophoresis AED Antiepileptic drug

2D-PAGE Two-dimensional polyacrylamide gel Ago2 Argonaute 2 mRNA endonuclease
electrophoresis AHA American Heart Association
5-HT 5-Hydroxytriptamine or serotonin AIDS Acquired immune deficiency syndrome
5-HTT 5-HT transporter AIMs Ancestry informative markers
5-HTTLPR 5-HTT gene-linked polymorphic region AJCC American Joint Committee on Cancer
6-MMP 6-Methylmercaptopurine ALL Acute lymphoblastic leukemia
6-MP 6-Mercaptopurine ALOX5AP Arachidonate 5-lipooxygenase-activating protein
6-MTIMP 6-Methyl-thioinosinemonophosphate AMACR Alpha methylacyl CoA reductase
6-TGN 6-Thioguanine nucleosides AML Acute myeloid leukemia
6-TIMP 6-Thioinosinemonophosphate AMR Antibody mediated rejection
AAU Acute anterior uveitis AOO Age of onset
ABCA1 Adenosine triphosphate-binding cassette Apo(a) Apolipoprotein(a)
protein A1 ApoE Apolipoprotein E
ABCB1 Adenosine triphosphate-binding cassette, APOE Apolipoprotein E (gene name)
sub-family B AR Androgen receptor
ABI Ankle brachial index AR Autosomal recessive
ACC American College of Cardiology ARACNe Algorithm for the Reconstruction of Accurate
ACE Angiotensin converting enzyme Cellular Networks
aCGH Array comparative genomic hybridization ARE Androgen response element
ACR Acute cellular rejection ARH Autosomal recessive hypercholesterolemia
AD Alzheimer’s disease ARJP Autosomal recessive juvenile Parkinsonism
AD Aortic dilation ARVC Arrhythmogenic right ventricular
ADH Autosomal dominant hypercholesterolemia cardiomyopathy
ADHD Attention deficit hyperactivity disorder AS Ankylosing spondylitis
ADIGE Autosomal dominant idiopathic generalized ASCA Anti-Saccharomyces cerevisiae antibodies
epilepsy ASCO American Society for Clinical Oncology
ADJME Autosomal dominant juvenile myoclonic ASCVD Atherosclerotic cardiovascular disease
epilepsy ASD Atrial septal defect
ADNFLE Autosomal dominant nocturnal frontal lobe ASO Anti-sense oligonucleotides
epilepsy ASPE Allele-specific primer extension
ADP Adenosine 5-diphosphate ATM Ataxia telangiectasia mutated
ADR Adverse drug reaction ATP Adenosine triphosphate

xi
xii ■ Abbreviations

ATP Adult Treatment Panel CFTR Cystic fibrosis transmembrane conductance

ATR Ataxia-telangiectasia and RAD3-related regulator
AZT Azidothymidine CGAP Cancer Genome Anatomy Project
CGH Comparative genomic hybridization
B1-AR 1-adrenergic receptor CGHa Comparative genomic hybridization array
BBB Blood–brain barrier CGP Cancer Genome Project
BCAA Branched-chain amino acids CHD Congenital heart disease
Bcl B-cell lymphoma protein CHD Coronary heart disease
BCL-2 B-cell lymphoma 2 CHF Congestive heart failure
Bcl-Abl Breakpoint cluster region – Abelson kinase CHMP Committee for Medicinal Products for Human
fusion protein Use
BDNF Brain-derived neurotrophic factor CHRNA4 Cholinergic receptor, nicotinic, alpha 4 (gene)
BER Base excision repair CIBEX Center for Information Biology Gene
BEST -Blocker Evaluation of Survival Trial Expression
BH Bcl-2 homology domain CIC Citrate/isocitrate carrier
BLAST Basic local alignment and search tool CICR Calcium-induced calcium release
BLAT BLAST-like alignment tool CKD Chronic kidney disease
BMC Bone marrow cell CLI Critical limb ischemia
BMI Body mass index CLIA Clinical Laboratory Improvement Amendments
BMP-7 Bone morphogenic protein-7 CML Chronic myelogenous leukemia
BOLD Blood oxygen level-dependent CMT Charcot-Marie-Tooth disease
BPDE Benzo (a) pyrene diol epoxide CMV Cytomegalovirus or human herpes virus 5
BPH Benign prostatic hypertrophy CNS Central nervous system
BRCA Breast cancer gene CNV Copy number variant
BRCA1 Breast cancer 1, early onset, protein COPA Cancer outlier profile analysis
BRCA2 Breast cancer type 2 susceptibility protein COR C-terminal of ROC domain
BRD2 Bromodomain containing 2 (gene) COX Cyclooxygenase
BSML Bioinformatic sequence markup language COX-2 Cyclooxygenase-2
CPOE Computerized provider order entry
CA Capsid (viral protein) CRC Colorectal cancer
CAD Coronary artery disease CREB Cyclic AMP response binding protein
CADASIL Cerebral autosomal dominant arteriopathy with CRF Circulating recombined form
subcortical infarcts and leukoencephalopathy CRP C-reactive protein
CAE Childhood absence epilepsy CS Cell signaling factor
CALGB Cancer and leukemia group B CSA Comparative sequence analysis
CAP College of American Pathologists CSF Cerebrospinal fluid
CARD Caspase recruitment domain (gene) CSF1 Colony stimulating factor 1
CARGO Cardiac Allograft Rejection Gene Expression CTC Circulating tumor cells
Observational study CTGF Connective tissue growth factor
CAV Cardiac allograft vasculopathy CTL Cytotoxic T lymphocytes
CBD Cortical basal degeneration CTLA Connective tissue late antigen
CBP CREB-binding protein CTSA Clinical and Translational Science Awards
CBZ Carbamazepine CX32 Connexin-32
CCD Charge coupled device CX37 Connexin-37
CCL Chemokine (C-C motif) ligand CYP Cytochrome P450
CCND1 Cyclin D1, a proto-oncogene CYP2C19 Cytochrome P450 2C19
CD Cluster of differentiation CYP2D6 Cytochrome P450 2D6
CD Crohn’s disease
CDAI Crohn’s disease activity index D2R Dopamine-2 receptor
CDC Centers for Disease Control DAI Disease Activity Score (for Ulcerative Colitis)
cDNA Complementary deoxyribonucleic acid dbSNP NCBI SNP database
CDS Clinical decision support DCM Dilated cardiomyopathy
CED-4 Cell death abnormality gene 4 DGGE Denaturing gradient gel electrophoresis
CETP Cholesteryl ester transfer protein DGI Diabetes Genetics/Initiative
CF Cystic fibrosis DHF Diastolic heart failure
 Abbreviations ■ xiii

DHLPC Denaturing high performance liquid FDB Familial defective apoB-100

chromatography FFPE Formalin-fixed, paraffin-embedded
DLB Diffuse Lewy body FGF Fibroblast growth factor
DLBD Diffuse Lewy body disease FGF-2 Fibroblast growth factor-2
DLDA Diagonalized linear discriminant analysis FH Familial hypercholesterolemia
DLG Disc large homologue (gene) FHTG Familial hypertriglyceridemia
DMEs Drug-metabolizing enzymes FISH Fluorescence in situ hybridization
DNA Deoxyribonucleic acid FKBP FK506-binding protein
DNase Deoxyribonuclease FL Follicular lymphoma
DNMTs DNA methyltransferases FLT-3 FMS-like tyrosine kinase-3
DOPAC Dihydroxyphenylacetic acid fMRI Functional MRI
ds Double stranded FNA Fine needle aspirate
dsRNA Double-stranded ribonucleic acid FOV Field of view
DTC Direct-to-consumer FSGS Focal segmental glomerulosclerosis
DU Duodenal ulcer FTD Frontotemporal dementia
DZ Dizygotic FUSION Finland–United States Investigation of NIDDM
genetics
EAE Experimental autoimmune encephalomyelitis
EBI European Bioinformatics Institute
GABBR1 GABA B receptor 1 (gene)
EBV Epstein–Barr virus
GABRG2 GABA A receptor, gamma 2 (gene)
ECL Eenterochromaffin-like cells
GAIN Genetic Association Information Network
ECM Extracellular matrix
GAPDH Glyceraldehyde-3-phosphate dehydrogenase
EDG-1 Endothelial differentiation gene-1
GBM Glomerular basement membrane
EGAPP Evaluation of Genomic Applications in Practice
GBS Guillain–Barre Syndrome
and Prevention
GCKR Glucokinase regulatory protein
EGF Epidermal growth factor
GC-MS Gas chromatography–mass spectrometry
EGFR Epidermal growth factor receptor
GCSF Granulocyte colony-stimulating factor
EHR Electronic health record
GDNF Glial cell line-derived neurotrophic factor
EIA Enzyme immunoassay
GEFS Generalized epilepsy with febrile seizures plus
EL Endothelial lipase
GEO Gene Expression Omnibus
ELISA Enzyme-linked immunosorbent assay
GEP Gene expression profiling
ELMO1 Engulfment and cell motility 1
GFAP Glial fibrillary acidic protein
EM Extracellular matrix protein
GFP Green fluorescent protein
EMB Endomyocardial biopsy
GLEPP1 Glomerular epithelial protein 1
EMBL-EBI European Molecular Biology Laboratory–
GLP Good laboratory practice
European Bioinformatics Institute
GM-CSF Granulocye macrophage–colony stimulating
EMEA European Medicines Evaluation Agency
factor
ENCODE Encyclopedia of DNA Elements
GO Gene ontology
EOAD Early-onset Alzheimer’s disease
GPI Globus pallidus interna
EPIYA Single letter codes for amino acids
GR Glucocorticoid receptor gene
eQTL Expression quantitative trait loci
GSEA Gene set enrichment analysis
ERK Extracellular signal-regulated kinase
GSIS Glucose-stimulated insulin secretion
ESR Erythrocyte sedimentation rate
GSTT Glutathione S-transferase
ESRD End-stage renal disease
GU Gastric ulcer
EST Expressed sequence tag
GWAS Genome-wide association study
FA Fanconi anemia GZM Granzyme
FACS Fluorescent-activated cell sorting
FANCA Fanconi anemia proteins A H Heterozygosity
FANCD2 Fanconi anemia protein D2 HAART Highly active anti-retroviral therapy
FAP Familial adenomatous polyposis HAV Hepatitis A
FCHL Familial combined hyperlipidemia HBV Hepatitis B
fCJD Familial Creutzfeldt–Jakob disease HCC Hepatocellular carcinoma
FCS Familial hyperchylomicronemia syndrome HCM Hypertrophic cardiomyopathy
FD Familial dysbetalipoproteinemia HCV Hepatitis C
FDA Food and Drug Administration (USA) HDAC Histone deacetylase
xiv ■ Abbreviations

HDL High-density lipoproteins IDO Indolemaine 2,3-dioxygenase

HDM2 Human double minute 2 IFN Interferon
HDV Hepatitis D IFN- Interferon-beta
HeLa Cervical cancer cell line IFN- Interferon-gamma
HEPS Highly exposed persistently seronegative Ig Immunoglobulin
individuals IgA Immunoglobulin-A
HER2 Human epidermal growth factor receptor 2 IGF-I Insulin-like growth factor-I
HEV Hepatitis E IHC Immunohistochemistry
HF Heart failure IHE Integrating the Healthcare Enterprise
HFPEF Heart failure with preserved ejection fraction IKBL Inhibitor of B-like (gene)
HGF Hepatocyte growth factor IL Interleukin
HGPRT Hypoxanthine phosphoribosyl transferase IL (4/13) Interleukin (4/13)
HHS Health and Human Services (U.S.) IL-1 Interleukin-1 beta (gene)
HHV-6 Human herpes virus 6 IL-1ra Interleukin-1 receptor antagonist
HITSP Healthcare Information Technology Standards IL-6 Interleukin-6
Panel IL-10 Interleukin-10
HIV Human immunodeficiency virus IMAGE Invasive Monitoring Attenuation through Gene
HKMT Histone lysine methyltransferases Expression study
HL Hepatic lipase iMC Immature myeloid cells
HL7 Health Level 7 IN Integrase (viral protein)
HLA/HLA Human leukocyte antigen/(gene) IOM Institute of Medicine (U.S.)
HLI Hind limb ischemia IS Insertion sequence
HMT Histone methyltransferase ISB Institute for Systems Biology
HNPCC Hereditary nonpolyposis colorectal cancer ISG Intreferon stimulated gene
HNSCC Head and neck squamous cell carcinoma ISHLT International Society for Heart and Lung
HP-1 Heterochromatin-associated protein-1 Transplantation
HPV Human papilloma virus IT Information technology
HPV-16 Human papilloma virus-16 IVDMIA In vitro diagnostic multivariate index assay
HR Homologous recombination
HRPC Hormone refractory prostate cancer JCA Juvenile chronic arthritis
HS Hyper-spectral JHDM1 JmjC domain-containing histone demethylase-1
HSC Hepatic stellate cell JME Juvenile myoclonic epilepsy
HSP Heat shock protein Kb Kilobase
HSV-1 Human herpes simplex virus type 1 KEGG Kyoto Encyclopedia of Genes and Genomes
HSV1-TK Herpes simplex virus type 1-thymidine kinase
HSV-2 Human herpes simplex virus type 2 LARGO Lung Allograft Rejection Gene expression
hTERT Human telomerase reverse transcriptase Observational study
HTLV-I Human T-cell leukemia/lymphoma virus type I LAV Lymphadenopathy-associated virus
HTLV-III Human T-cells lymphotropic virus type 3 LB Lewy body
HTS High-throughput screening LCAT Lecithin cholesterol acyltransferase
HVJ Hemagglutinating virus of Japan LCM Laser capture microdissection
LD Linkage disequilibrium
IBD Inflammatory bowel disease LDL Low-density lipoproteins
IBDQ Inflammatory bowel disease questionnaire l -DOPA Levodopa
IC Intermittent claudication LOAD Late-onset Alzheimer’s disease
IC Interstitial cystitis LOD Logarithm of the odds
ICAM Intracellular adhesion molecules LOH Loss of heterozygosity
ICD Implantable cardioverter defibrillator LOINC Logical Observation Identifiers, Names, and
ICD International Classification of Diseases Codes
ICDc Cytosolic, NADP-dependent isocitrate LOR Line of response
dehydrogenase Lp(a) Lipoprotein(a)
iDC Immature dendritic cells LPA Lysophosphatidic acid
IDCM Idiopathic dilated cardiomyopathy LPL Lipoprotein lipase
IDDM Insulin-dependent diabetes mellitus LPS Lipopolysaccharide
IDL Intermediate-density lipoproteins LRR Leucine-rich repeat
 Abbreviations ■ xv

LRRK2 Leucine rich repeat kinase 2 MITF Microphthalmia transcription factor

LSD1 Lysine-specific demethylase-1 MLEM Maximum likelihood expectation maximization
LTA Lymphotoxin alpha MLPA Multiplex ligation-dependent probe
LTA4H Leukotriene A4 hydrolase amplification
LTB4 Leukotriene B4 MMP Matrix metalloproteinase
LTNP Long-term non-progression MMP-3 Matrix metalloproteinase-3
LV Left ventricle MMR Mismatch repair
LVAD Left ventricular assist device MPSS Massively parallel signature sequencing
LVEDP Left ventricular end-diastolic pressure MPTP 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine
LVEF Left ventricular ejection fraction mQTL Metabolite quantitative trait loci
LVH Left ventricular hypertrophy mRNA Messenger ribonucleic acid
LVOT(O) Left ventricular outflow tract (obstruction) mRSS Modified Rodnan Skin Score
MS Multiple sclerosis
MA Matrix (viral protein) MS Multispectral
mAb Monoclonal antibodies MS/MS Tandem mass spectrometry
MADH6 Mothers against decapentaplegic homolog 6 MSA Multiple system atrophy
MAGE-ML MicroArray and Gene Expression Markup MTDNA Mitochondrial DNA
Language MTHFR Methylenetetrahydrofolate reductase (gene)
MAGUK Membrane-associated guanylate kinase mTOR Mammalian target of rapamycin
MAM Metastasis-averse microenvironment MTP Microsomal triglyceride transfer protein
MAO Monoamine oxidase MTX Methotrexate
MAOA Monoamine oxidate A MudPIT Multidimensional protein identification
MAP Mitogen-activated protein technology
MAPK Microtubule-associated protein kinase MVP Mitral valve prolapse
MAPK Mitogen-activated protein kinase MZ Monozygotic
MAQC Microarray quality control
Mb Megabase NAAT Nucleic acid amplification testing
MBD Methylated DNA binding domain protein NAD(P)H Nicotinamide adenine dinucleotide phosphate
MCD Malonyl CoA decarboxylase reduced form
MCD Minimal change disease NAFLD Non-alcoholic fatty liver disease
MCP Monocyte/macrophage chemoattractant NASH Non-alcoholic steatohepatitis
protein NAT2 N-Acetyltransferase 2
MCP-1 Monocyte chemoattractant protein 1 NAWM Normal appearing white matter
MCS Multi-species conserved sequence NC Nucleocapsid (viral protein)
M-CSF Macrophage colony-stimulating factor N-CAM Neural cell adhesion molecule
MDM2 Mouse double minute 2 NCBI National Center for Biotechnology
MDP Muramyl dipeptide Information
MDR Multidrug resistance (gene) NCE New chemical entity
MedDRA Medical Dictionary for Regulatory Activities NCEP National Cholesterol Education Program
Terminology NCI60 Refers to a set of 60 cancer cell lines curated at
MEF2A Myocyte-enhancing factor 2A the NCI (National Cancer Institute)
Megsin Mesangial cell-specific gene with homology ncRNA Non-coding RNA
to serpin NEF NEgative regulatory Factor (viral protein)
MEN Multiple endocrine neoplasm NER Nucleotide excision repair
MeSH Medical Subject Headings NF1/2 Neurofibromatosis1/2
MeV Multiexperiment viewer NHGRI National Human Genome Research Institute
MGED Microarray Gene Expression Data society NHR Non-homologous recombination
MGMT O6-Methylguanine-DNA methyltransferase NIEHS National Institute of Environmental Health
MHC Major histocompatability complex Sciences (NIH)
MI Myocardial infarction NIH National Institutes of Health
MIAME Minimal Information About a Microarray NK Natural killer
Experiment NMR Nuclear magnetic resonance
MIM Metastasis-inclined microenvironment NNRTI Non-nucleosidic reverse transcriptase inhibitor
miR-192 MicroRNA-192 NOD Nucleotide oligomerization domain (gene)
miRNA Micro-ribonucleic acid NPV Negative predictive value
xvi ■ Abbreviations

NQO1 Nicotinamide adenine dinucleotide phosphate PI3K Phosphotidylinositol triphosphate kinase

oxidoreductase PIN Prostatic intraepithelial neoplasia
NRTI Nucleosidic reverse transcriptase inhibitor PK Pharmacokinetics
NSAID Non-steroidal anti-inflammatory drug PLTP Phospholipid transfer protein
nt Nucleotides PMAGE Polony Multiplex Analysis of Gene
NUD Non-ulcer dyspepsia Expression
NYHA New York Heart Association PMBC Peripheral blood mononuclear cells
PML-RAR Pro-myelocytic leukemia retinoic acid
OBO Open Biomedical Ontologies receptor oncoprotein
OCTN Organic cation transporter (gene) PON1 Paraoxonase
OHCA Out of hospital cardiac arrest PPI Percutaneous peripheral intervention
OMIM Online Mendelian Inheritance in Man PPV Positive predictive value
OMP Outer membrane protein PR Protease (viral)
OmpC Outer membrane porin C of E. coli PrEC Prostate epithelial cells
opn Osteopontin (gene) PRIDE Proteomics Identifications Database
OPN Osteopontin (protein) PRNP Prion protein (gene)
OR odds ratio PS Pulmonary stenosis
ORESTES Open reading frame expressed sequence tags PSA Prostate-specific antigen
ORF Open reading frame PsA Psoriatic arthritis
OSEM Ordered subset expectation maximization PSC Primary sclerosing cholangitis
PSP Progressive supranuclear palsy
p53BP1 p53 Binding protein 1 PTEN Phosphatase and tensin homolog
PAD Peripheral arterial disease PTM Pre-trans-splicing molecule
PAGE Polyacrylamide gel electrophoresis PUD Peptic ulcer disease
PAI Pathogenicity island PZ Plasticity zone
PAM Prediction analysis of microarrays
QPCR Quantitative PCR
pANCA Perinuclear antineutrophil cytoplasmatic
qRT Quantitative real-time PCR
antibodies
qRT-PCR Quantitative reverse-transcriptase polymer-
PAOD1 Peripheral arterial occlusive disease
ase chain reaction
Pap Papanicolaou
QTL Quantitative trait locus
Parvo B19 Human parvovirus B-19
QT-PCR Quantitative real-time polymerase chain
PBC Primary biliary cirrhosis
reaction
PBL Peripheral blood lymphocytes
QV Quality value
PBMC Peripheral blood mononuclear cell
PC Pyruvate carboxylase R&D Research and Development
PCA Principal components analysis RA Rheumatoid arthritis
PCNA Proliferating cell nuclear antigen RAAS Renin-angiotensin-aldosterone system
PCR Polymerase chain reaction RAPD-PCR Random amplified polymorphic deoxyri-
PCSK9 Proprotein convertase subtilisin/kexin type 9 bonucleic acid–polymerase chain reaction
PCV Procarbazine/CCNU/vincristine RB Retinoblastoma
PD Parkinson disease RB Retinoblastoma (gene)
PD Pharmacodynamic RCM Restrictive cardiomyopathy
PDA Patent ductus arteriosus REPAIR-AMI Reinfusion of enriched progenitor cells
PDA Personal digital assistant and infarct remodeling in acute myocardial
PDD Parkinson disease with dementia infarction
PDGF Platelet-derived growth factor RET Ret proto-oncogene
PDGFR Platelet-derived growth factor receptor REV REgulator of Virion protein expression
PDH Pyruvate dehydrogenase (viral protein)
PDTC Pyrrolidine dithiocarbamate RFLP Restriction fragment length polymorphism
PDYN prodynorphin (gene) RISC RNA interference silencing complex
PFGE Pulse field gel electrophoresis RNA Ribonucleic acid
PGE2 Prostaglandin E2 RNAi Ribonucleic acid interference
PGx Pharmacogenetics and pharmacogenomics ROC RAS in complex proteins
PHT Phenytoin ROCO ROC (RAS of complex proteins)/COR
PI Protease inhibitor (C-terminal of ROC)
 Abbreviations ■ xvii

ROS Reactive oxygen species SOX10 SRY-box containing gene 10

RP Rapid progression SpA Spondyloarthropathy
RPA Ribonuclease protection assay SPARC Secreted protein, acidic, and rich in cysteine,
RSV Respiratory syncytial virus osteonectin
RT Reverse transcriptase (viral protein) SPMS Secondary progressive MS
RT-PCR Real-time polymerase chain reaction SR-BI Scavenger receptor, class BI
RT-PCR Reverse transcription – polymerase chain ss Single-stranded
reaction SSc Systemic sclerosis
RV Right ventricle SSCP Single strand conformation polymorphism
RVHF Right ventricular heart failure SSRP Simple sequence repeat polymorphism
SSTR2 Somatostatin receptor type 2
SACGHS Secretary’s Advisory Committee on STAT Signal transducers and activators of
Genetics, Health and Society (U.S.) transcription
SAGE Serial Analysis of Gene Expression STEMI ST segment Elevation Myocardial Infarction
SALSA Scoring algorithm for spectral analysis STK11 gene Serine/threonine kinase 11
SAM S-Adenosyl-l -methionine (AdoMet) STN Subthalmic nucleus
SAM Significance analysis of microarrays SU Surface (viral protein)
SAM Systolic anterior motion of mitral valve SVAS Supravalvar aortic stenosis
SAP/Exo I Shrimp alkaline phosphatase/exonuclease I SVR Sustained viral response
SARS Severe acute respiratory syndrome SWOG Southwest Oncology Group
SBE Single-base extension
TAM Tumor associated macrophages
SCD Sudden cardiac death
TAT TransActivator of Transcription (viral
SCID Severe combined immunodeficiency
protein)
SCN1A Voltage-gated sodium channel, type 1, alpha
TBB Transcriptomic-based biomarkers
subunit (gene)
TCF7L2 Transcription factor 7-like 2
SCOTS Selective capture of transcribed
TCR T-cell receptor
sequences
TDM Therapeutic drug monitoring
SCX Strong cation exchange
TF Transcription factor
SD Standard deviation
TFAP2B Transcription factor activating protein 2
SDO Standards development organization
TGF Transforming growth factor
SE Shared epitope of HLA (human leukocyte
TGF- Transforming growth factor beta
antigen) genes
TH Tyrosine hydroxylase
SE Spongiform encephalopathies
Th1 T-helper cell, type 1
SEBASTIAN System for Evidence-Based Advice
Th2 T-helper cell, type 2
through Simultaneous Transaction with an
TIGR The Institute for Genomic Research
Intelligent Agent across a Network
TIMP Tissue inhibitor of metalloproteinase
SEC Sinusoidal endothelial cell
TIMP-1 Tissue inhibitor of metalloproteinase-1
SERPA Serological proteome analysis
TK Tyrosine kinase
SHF Systolic heart failure
TLE Temporal lobe epilepsy
shRNA Short hairpin ribonucleic acid
TLR Toll-like receptor
SIP1 Smad-interacting protein 1
TLS Trans-lesion DNA synthesis
siRNA Small interfering ribonucleic acid
TM Trans-Membrane (viral protein)
SIV Simian immunodeficiency virus
TNF Tumor necrosis factor
SJS/TEN Stevens–Johnson syndrome/toxic epidermal
TNF- Tumor necrosis factor-alpha
necrolysis
TNF- Tumor necrosis factor-beta
SLC12A3 Solute carrier family 12 member 3
TNM Tumor-node-metastasis stage
SLE Systemic lupus erythematosus
TOF Tetralogy of Fallot
SLN Sentinel lymph node
TPMT/TPMT Thiopurine methyl transferase/(gene)
SMD Stanford Microarray Database
SN Substantia nigra Treg Regulatory T-cells
SNOMED CT Systematized Nomenclature of Medicine, TSA Trichostatin A
TSG Tumor suppressor gene
Clinical Terms
TSP Thrombospondin
SNP Single nucleotide polymorphism
SNpc Substantia nigra pars compacta UADT Upper aerodigestive tract
SNR Substantia nigra pars reticulata UC Ulcerative colitis
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