Essentials of Genomic and Personalized Medicine

Table of Contents

Cover image

Copyright

Preface

Abbreviations

Contributors

Chapter 1. The Foundations of Genomic and Personalized Medicine

Chapter 2. Organization, Variation and Expression of the Human Genome

Chapter 3. DNA Sequencing for the Detection of Human Genome Variation

Chapter 4. Genome-Wide Association Studies and Genotyping Technologies

Chapter 5. Copy Number Variation and Human Health

Chapter 6. DNA Methylation Analysis

Chapter 7. DNA Microarrays in Biological Discovery and Patient Care

Chapter 8. Proteomics

Chapter 9. Comprehensive Metabolic Analysis for Understanding of Disease

Chapter 10. Bioinformatic and Computational Analysis for Genomic Medicine

Chapter 11. Systems Biology and Systems Medicine

Chapter 12. Electronic Medical Records in Genomic Medicine Practice and Research

Chapter 13. Online Health Information Retrieval by Consumers

Chapter 14. Translational Genomics

Chapter 15. Pharmacogenetics and Pharmacogenomics

Chapter 16. Clinical Implementation of Translational Genomics

Chapter 17. The Role of Genomics in Enabling Prospective Health Care

Chapter 18. Genome Policy Considerations for Genomic Medicine

Chapter 19. Federal Regulation of Genomic Medicine

Chapter 20. Economic Issues and Genomic Medicine

Chapter 21. Public Health Genomics

Chapter 22. The Genomics of Hypertension

Chapter 23. Lipoprotein Disorders

Chapter 24. Genomics of Myocardial Infarction

Chapter 25. Acute Coronary Syndromes

Chapter 26. Heart Failure in the Era of Genomic Medicine

Chapter 27. Genomic Assessment of Cardiac Transplant Rejection

Chapter 28. Genetics and Genomics of Hypertrophic Cardiomyopathy

Chapter 29. Genetics and Genomics of Arrhythmias

Chapter 30. Genetics and Genomics in the Management of Hemostasis and Thrombosis

Chapter 31. Genomics of Congenital Heart Disease

Chapter 32. Genomics in the Management of Lymphomas

Chapter 33. Genomics in Leukemias

Chapter 34. Genomics in the Diagnosis and Management of Lung Cancer

Chapter 35. Genomics in the Diagnosis and Management of Breast Cancer

Chapter 36. Colorectal Cancer

Chapter 37. Genomic Evaluation and Management of Prostate Cancer

Chapter 38. Genomic Assessment of Ovarian Cancer

Chapter 39. Genomic Evaluation of Pancreatic Neoplasms

Chapter 40. Genomic Evaluation of Head and Neck Cancer

Chapter 41. Genomic Evaluation of Brain Tumors and Gliomas

Chapter 42. Targeted Therapies for Cancer

Chapter 43. Genomics in the Evaluation and Management of Rheumatoid Arthritis

Chapter 44. Genomic Evaluation of Multiple Sclerosis

Chapter 45. Genomic Assessment of Inflammatory Bowel Disease

Chapter 46. Asthma Genomics

Chapter 47. Genomics in the Evaluation and Management of Chronic Obstructive Pulmonary Disease

Chapter 48. Genetics and Genomics of Interstitial Lung Disease

Chapter 49. Peptic Ulcer Disease

Chapter 50. Genomics in Pathogenesis of Cirrhosis

Chapter 51. Genomic Medicine and Obesity

Chapter 52. Diabetes

Chapter 53. Genetics and Genomics of Dementia

Chapter 54. Genetics and Genomics of Parkinson's Disease

Chapter 55. Genomic Considerations in Ophthalmology

Chapter 56. Genomics in the Diagnosis and Management of Depression

Chapter 57. Genomic Approaches to the Host Response to Pathogens

Chapter 58. Host Genomics and Bacterial Infections

Chapter 59. Genomics in the Evaluation and Management of Sepsis

Chapter 60. Genomics and the Management of Hepatitis

Index

Copyright

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Preface

Geoffrey S. Ginsburg, M.D., Ph.D.

Huntington F. Willard, Ph.D.

With the completion of the Human Genome Project at the beginning of this decade and the rapid development and application of new advances in our ability to understand and query the human genome and its gene set, it is time already to review the early sketches of a much-anticipated transformation of the practice of medicine. We have seen the very first signs of a fundamental shift in how we behold human physiology and pathology, how we view the concept of what is normal, how we consider individuals and their prospects for lifelong health, and how we design health care systems that are equally adaptable to the demands of population-wide epidemics and the opportunities for personalized care that utilizes genome-based information to consider individual susceptibility to disease and therapeutic options.

Genome-based data, information, knowledge, and eventually wisdom will make possible the kind of health care that has been dreamed of since the advent of disease-based medicine early in the 20th century. A system of health care that harnesses the data intensity of the genome and its derivatives, along with imaging, clinical, and environmental information, will empower physicians and other health care providers to do what they have always aspired to do – make medical care as individualized as possible. But this newfound information and knowledge will also allow each of us as consumers of health care to take more control of our futures and to develop a more strategic and prospective approach to health. We stand at the dawn of a profound change in science and medicine's predictive nature and in our understanding of the biological underpinnings of health and disease. Even in this early light, we can see the outlines of a coming ability to:

● predict individual susceptibility to disease, based on genetic, genomic, and other factors;

● provide more useful tools and individualized programs for disease prevention, based on knowledge of one's susceptibility;

● detect the onset of disease earlier and before it is clinically evident, based on newly discovered biological markers that arise from changes at the molecular level;

● preempt disease progression, as a result of early detection; and

● target medicines and their dose more precisely and safely to each patient, on the basis of a deep understanding of disease mechanism and the role that genetic and genomic factors play in the individual response to drugs.

The time for this revolution in genomic and personalized medicine has come. As its name suggests, this book is intended to lay out the essentials of this new approach to medicine and to emphasize for particular conditions the clinical opportunities that present themselves today. It is designed to complement the more comprehensive two-volume book Genomic and Personalized Medicine, published last year, which presented in substantial depth the foundations of this new science, outlined the early opportunities for the practice of medicine to incorporate genome-based analysis into health care, and anticipated the many conditions to which genomic and personalized medicine will apply in the years ahead.

This volume on Essentials of Genomic and Personalized Medicine describes an emerging field that spans the breadth of clinical medicine, with many challenges for society at large and for health care systems in particular. Nonetheless, we are optimistic that the appropriate delivery models and economic incentives will be developed in a trustworthy framework that will be embraced by societies around the globe.

Our intended audience is clinically oriented but broad, ranging from medical students to residents and fellows to practitioners in any of the health care professions – physicians in any of the medical specialties, surgeons, nurses, genetic (and genomic) counselors, and laboratory directors.

In times of transformation, we are all students. We hope that this Essentials volume will help usher in this new era of genomic and personalized medicine and will provide a useful and thorough introduction to the science and practice of this new approach to human health.

June 2009

Abbreviations

2D-DIGE

Two-dimensional difference gel electrophoresis

2D-PAGE

Two-dimensional polyacrylamide gel electrophoresis

5-HT

5-Hydroxytriptamine or serotonin

5-HTT

5-HT transporter

5-HTTLPR

5-HTT gene-linked polymorphic region

6-MMP

6-Methylmercaptopurine

6-MP

6-Mercaptopurine

6-MTIMP

6-Methyl-thioinosinemonophosphate

6-TGN

6-Thioguanine nucleosides

6-TIMP

6-Thioinosinemonophosphate

AAU

Acute anterior uveitis

ABCA1

Adenosine triphosphate-binding cassette protein A1

ABCB1

Adenosine triphosphate-binding cassette, sub-family B

ABI

Ankle brachial index

ACC

American College of Cardiology

ACE

Angiotensin converting enzyme

aCGH

Array comparative genomic hybridization

ACR

Acute cellular rejection

AD

Alzheimer's disease

AD

Aortic dilation

ADH

Autosomal dominant hypercholesterolemia

ADHD

Attention deficit hyperactivity disorder

ADIGE

Autosomal dominant idiopathic generalized epilepsy

ADJME

Autosomal dominant juvenile myoclonic epilepsy

ADNFLE

Autosomal dominant nocturnal frontal lobe epilepsy

ADP

Adenosine 5-diphosphate

ADR

Adverse drug reaction

AED

Antiepileptic drug

Ago2

Argonaute 2 mRNA endonuclease

AHA

American Heart Association

AIDS

Acquired immune deficiency syndrome

AIMs

Ancestry informative markers

AJCC

American Joint Committee on Cancer

ALL

Acute lymphoblastic leukemia

ALOX5AP

Arachidonate 5-lipooxygenase-activating protein

AMACR

Alpha methylacyl CoA reductase

AML

Acute myeloid leukemia

AMR

Antibody mediated rejection

AOO

Age of onset

Apo(a)

Apolipoprotein(a)

ApoE

Apolipoprotein E

APOE

Apolipoprotein E (gene name)

AR

Androgen receptor

AR

Autosomal recessive

ARACNe

Algorithm for the Reconstruction of Accurate Cellular Networks

ARE

Androgen response element

ARH

Autosomal recessive hypercholesterolemia

ARJP

Autosomal recessive juvenile Parkinsonism

ARVC

Arrhythmogenic right ventricular cardiomyopathy

AS

Ankylosing spondylitis

ASCA

Anti- Saccharomyces cerevisiae antibodies

ASCO

American Society for Clinical Oncology

ASCVD

Atherosclerotic cardiovascular disease

ASD

Atrial septal defect

ASO

Anti-sense oligonucleotides

ASPE

Allele-specific primer extension

ATM

Ataxia telangiectasia mutated

ATP

Adenosine triphosphate

ATP

Adult Treatment Panel

ATR

Ataxia-telangiectasia and RAD3-related

AZT

Azidothymidine

B1-AR

β1-adrenergic receptor

BBB

Blood–brain barrier

BCAA

Branched-chain amino acids

Bcl

B-cell lymphoma protein

BCL-2

B-cell lymphoma 2

Bcl-Abl

Breakpoint cluster region – Abelson kinase fusion protein

BDNF

Brain-derived neurotrophic factor

BER

Base excision repair

BEST

β-Blocker Evaluation of Survival Trial

BH

Bcl-2 homology domain

BLAST

Basic local alignment and search tool

BLAT

BLAST-like alignment tool

BMC

Bone marrow cell

BMI

Body mass index

BMP-7

Bone morphogenic protein-7

BOLD

Blood oxygen level-dependent

BPDE

Benzo (a) pyrene diol epoxide

BPH

Benign prostatic hypertrophy

BRCA

Breast cancer gene

BRCA1

Breast cancer 1, early onset, protein

BRCA2

Breast cancer type 2 susceptibility protein

BRD2

Bromodomain containing 2 (gene)

BSML

Bioinformatic sequence markup language

CA

Capsid (viral protein)

CAD

Coronary artery disease

CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy

CAE

Childhood absence epilepsy

CALGB

Cancer and leukemia group B

CAP

College of American Pathologists

CARD

Caspase recruitment domain (gene)

CARGO

Cardiac Allograft Rejection Gene Expression Observational study

CAV

Cardiac allograft vasculopathy

CBD

Cortical basal degeneration

CBP

CREB-binding protein

CBZ

Carbamazepine

CCD

Charge coupled device

CCL

Chemokine (C-C motif) ligand

CCND1

Cyclin D1, a proto-oncogene

CD

Cluster of differentiation

CD

Crohn's disease

CDAI

Crohn's disease activity index

CDC

Centers for Disease Control

cDNA

Complementary deoxyribonucleic acid

CDS

Clinical decision support

CED-4

Cell death abnormality gene 4

CETP

Cholesteryl ester transfer protein

CF

Cystic fibrosis

CFTR

Cystic fibrosis transmembrane conductance regulator

CGAP

Cancer Genome Anatomy Project

CGH

Comparative genomic hybridization

CGHa

Comparative genomic hybridization array

CGP

Cancer Genome Project

CHD

Congenital heart disease

CHD

Coronary heart disease

CHF

Congestive heart failure

CHMP

Committee for Medicinal Products for Human Use

CHRNA4

Cholinergic receptor, nicotinic, alpha 4 (gene)

CIBEX

Center for Information Biology Gene Expression

CIC

Citrate/isocitrate carrier

CICR

Calcium-induced calcium release

CKD

Chronic kidney disease

CLI

Critical limb ischemia

CLIA

Clinical Laboratory Improvement Amendments

CML

Chronic myelogenous leukemia

CMT

Charcot-Marie-Tooth disease

CMV

Cytomegalovirus or human herpes virus 5

CNS

Central nervous system

CNV

Copy number variant

COPA

Cancer outlier profile analysis

COR

C-terminal of ROC domain

COX

Cyclooxygenase

COX-2

Cyclooxygenase-2

CPOE

Computerized provider order entry

CRC

Colorectal cancer

CREB

Cyclic AMP response binding protein

CRF

Circulating recombined form

CRP

C-reactive protein

CS

Cell signaling factor

CSA

Comparative sequence analysis

CSF

Cerebrospinal fluid

CSF1

Colony stimulating factor 1

CTC

Circulating tumor cells

CTGF

Connective tissue growth factor

CTL

Cytotoxic T lymphocytes

CTLA

Connective tissue late antigen

CTSA

Clinical and Translational Science Awards

CX32

Connexin-32

CX37

Connexin-37

CYP

Cytochrome P450

CYP2C19

Cytochrome P450 2C19

CYP2D6

Cytochrome P450 2D6

D2R

Dopamine-2 receptor

DAI

Disease Activity Score (for Ulcerative Colitis)

dbSNP

NCBI SNP database

DCM

Dilated cardiomyopathy

DGGE

Denaturing gradient gel electrophoresis

DGI

Diabetes genetics/initiative

DHF

Diastolic heart failure

DHLPC

Denaturing high performance liquid chromatography

DLB

Diffuse Lewy body

DLBD

Diffuse Lewy body disease

DLDA

Diagonalized linear discriminant analysis

DLG

Disc large homologue (gene)

DMEs

Drug-metabolizing enzymes

DNA

Deoxyribonucleic acid

DNase

Deoxyribonuclease

DNMTs

DNA methyltransferases

DOPAC

Dihydroxyphenylacetic acid

ds

Double stranded

dsRNA

Double-stranded ribonucleic acid

DTC

Direct-to-consumer

DU

Duodenal ulcer

DZ

Dizygotic

EAE

Experimental autoimmune encephalomyelitis

EBI

European Bioinformatics Institute

EBV

Epstein–Barr virus

ECL

Eenterochromaffin-like cells

ECM

Extracellular matrix

EDG-1

Endothelial differentiation gene-1

EGAPP

Evaluation of Genomic Applications in Practice and Prevention

EGF

Epidermal growth factor

EGFR

Epidermal growth factor receptor

EHR

Electronic health record

EIA

Enzyme immunoassay

EL

Endothelial lipase

ELISA

Enzyme-linked immunosorbent assay

ELMO1

Engulfment and cell motility 1

EM

Extracellular matrix protein

EMB

Endomyocardial biopsy

EMBL-EBI

European Molecular Biology Laboratory–European Bioinformatics Institute

EMEA

European Medicines Evaluation Agency

ENCODE

Encyclopedia of DNA Elements

EOAD

Early-onset Alzheimer's disease

EPIYA

Single letter codes for amino acids

eQTL

Expression quantitative trait loci

ERK

Extracellular signal-regulated kinase

ESR

Erythrocyte sedimentation rate

ESRD

End-stage renal disease

EST

Expressed sequence tag

FA

Fanconi anemia

FACS

Fluorescent-activated cell sorting

FANCA

Fanconi anemia proteins A

FANCD2

Fanconi anemia protein D2

FAP

Familial adenomatous polyposis

FCHL

Familial combined hyperlipidemia

fCJD

Familial Creutzfeldt–Jakob disease

FCS

Familial hyperchylomicronemia syndrome

FD

Familial dysbetalipoproteinemia

FDA

Food and Drug Administration (USA)

FDB

Familial defective apoB-100

FFPE

Formalin-fixed, paraffin-embedded

FGF

Fibroblast growth factor

FGF-2

Fibroblast growth factor-2

FH

Familial hypercholesterolemia

FHTG

Familial hypertriglyceridemia

FISH

Fluorescence in situ hybridization

FKBP

FK506-binding protein

FL

Follicular lymphoma

FLT-3

FMS-like tyrosine kinase-3

fMRI

Functional MRI

FNA

Fine needle aspirate

FOV

Field of view

FSGS

Focal segmental glomerulosclerosis

FTD

Frontotemporal dementia

FUSION

Finland–United States Investigation of NIDDM genetics

GABBR1

GABA B receptor 1 (gene)

GABRG2

GABA A receptor, gamma 2 (gene)

GAIN

Genetic Association Information Network

GAPDH

Glyceraldehyde-3-phosphate dehydrogenase

GBM

Glomerular basement membrane

GBS

Guillain–Barre Syndrome

GCKR

Glucokinase regulatory protein

GC-MS

Gas chromatography–mass spectrometry

GCSF

Granulocyte colony-stimulating factor

GDNF

Glial cell line-derived neurotrophic factor

GEFS+

Generalized epilepsy with febrile seizures plus

GEO

Gene Expression Omnibus

GEP

Gene expression profiling

GFAP

Glial fibrillary acidic protein

GFP

Green fluorescent protein

GLEPP1

Glomerular epithelial protein 1

GLP

Good laboratory practice

GM-CSF

Granulocye macrophage–colony stimulating factor

GO

Gene ontology

GPI

Globus pallidus interna

GR

Glucocorticoid receptor gene

GSEA

Gene set enrichment analysis

GSIS

Glucose-stimulated insulin secretion

GSTT

Glutathione S-transferase

GU

Gastric ulcer

GWAS

Genome-wide association study

GZM

Granzyme

H

Heterozygosity

HAART

Highly active anti-retroviral therapy

HAV

Hepatitis A

HBV

Hepatitis B

HCC

Hepatocellular carcinoma

HCM

Hypertrophic cardiomyopathy

HCV

Hepatitis C

HDAC

Histone deacetylase

HDL

High-density lipoproteins

HDM2

Human double minute 2

HDV

Hepatitis D

HeLa

Cervical cancer cell line

HEPS

Highly exposed persistently seronegative individuals

HER2

Human epidermal growth factor receptor 2

HEV

Hepatitis E

HF

Heart failure

HFPEF

Heart failure with preserved ejection fraction

HGF

Hepatocyte growth factor

HGPRT

Hypoxanthine phosphoribosyl transferase

HHS

Health and Human Services (U.S.)

HHV-6

Human herpes virus 6

HITSP

Healthcare Information Technology Standards Panel

HIV

Human immunodeficiency virus

HKMT

Histone lysine methyltransferases

HL

Hepatic lipase

HL7

Health Level 7

HLA/ HLA

Human leukocyte antigen/(gene)

HLI

Hind limb ischemia

HMT

Histone methyltransferase

HNPCC

Hereditary nonpolyposis colorectal cancer

HNSCC

Head and neck squamous cell carcinoma

HP-1

Heterochromatin-associated protein-1

HPV

Human papilloma virus

HPV-16

Human papilloma virus-16

HR

Homologous recombination

HRPC

Hormone refractory prostate cancer

HS

Hyper-spectral

HSC

Hepatic stellate cell

HSP

Heat shock protein

HSV-1

Human herpes simplex virus type 1

HSV1-TK

Herpes simplex virus type 1-thymidine kinase

HSV-2

Human herpes simplex virus type 2

hTERT

Human telomerase reverse transcriptase

HTLV-I

Human T-cell leukemia/lymphoma virus type I

HTLV-III

Human T-cells lymphotropic virus type 3

HTS

High-throughput screening

HVJ

Hemagglutinating virus of Japan

IBD

Inflammatory bowel disease

IBDQ

Inflammatory bowel disease questionnaire

IC

Intermittent claudication

IC

Interstitial cystitis

ICAM

Intracellular adhesion molecules

ICD

Implantable cardioverter defibrillator

ICD

International Classification of Diseases

ICDc

Cytosolic, NADP-dependent isocitrate dehydrogenase

iDC

Immature dendritic cells

IDCM

Idiopathic dilated cardiomyopathy

IDDM

Insulin-dependent diabetes mellitus

IDL

Intermediate-density lipoproteins

IDO

Indolemaine 2,3-dioxygenase

IFN

Interferon

IFN-β

Interferon-beta

IFN-γ

Interferon-gamma

Ig

Immunoglobulin

IgA

Immunoglobulin-A

IGF-I

Insulin-like growth factor-I

IHC

Immunohistochemistry

IHE

Integrating the Healthcare Enterprise

IKBL

Inhibitor of κB-like (gene)

IL

Interleukin

IL (4/13)

Interleukin (4/13)

IL-1β

Interleukin-1 beta (gene)

IL-1ra

Interleukin-1 receptor antagonist

IL-6

Interleukin-6

IL-10

Interleukin-10

IMAGE

Invasive Monitoring Attenuation through Gene Expression study

iMC

Immature myeloid cells

IN

Integrase (viral protein)

IOM

Institute of Medicine (U.S.)

IS

Insertion sequence

ISB

Institute for Systems Biology

ISG

Intreferon stimulated gene

ISHLT

International Society for Heart and Lung Transplantation

IT

Information technology

IVDMIA

In vitro diagnostic multivariate index assay

JCA

Juvenile chronic arthritis

JHDM1

JmjC domain-containing histone demethylase-1

JME

Juvenile myoclonic epilepsy

Kb

Kilobase

KEGG

Kyoto Encyclopedia of Genes and Genomes

LARGO

Lung Allograft Rejection Gene expression Observational study

LAV

Lymphadenopathy-associated virus

LB

Lewy body

LCAT

Lecithin cholesterol acyltransferase

LCM

Laser capture microdissection

LD

Linkage disequilibrium

LDL

Low-density lipoproteins

l-DOPA

Levodopa

LOAD

Late-onset Alzheimer's disease

LOD

Logarithm of the odds

LOH

Loss of heterozygosity

LOINC

Logical Observation Identifiers, Names, and Codes

LOR

Line of response

Lp(a)

Lipoprotein(a)

LPA

Lysophosphatidic acid

LPL

Lipoprotein lipase

LPS

Lipopolysaccharide

LRR

Leucine-rich repeat

LRRK2

Leucine rich repeat kinase 2

LSD1

Lysine-specific demethylase-1

LTA

Lymphotoxin alpha

LTA4H

Leukotriene A4 hydrolase

LTB4

Leukotriene B4

LTNP

Long-term non-progression

LV

Left ventricle

LVAD

Left ventricular assist device

LVEDP

Left ventricular end-diastolic pressure

LVEF

Left ventricular ejection fraction

LVH

Left ventricular hypertrophy

LVOT(O)

Left ventricular outflow tract (obstruction)

MA

Matrix (viral protein)

mAb

Monoclonal antibodies

MADH6

Mothers against decapentaplegic homolog 6

MAGE-ML

MicroArray and Gene Expression Markup Language

MAGUK

Membrane-associated guanylate kinase

MAM

Metastasis-averse microenvironment

MAO

Monoamine oxidase

MAOA

Monoamine oxidate A

MAP

Mitogen-activated protein

MAPK

Microtubule-associated protein kinase

MAPK

Mitogen-activated protein kinase

MAQC

Microarray quality control

Mb

Megabase

MBD

Methylated DNA binding domain protein

MCD

Malonyl CoA decarboxylase

MCD

Minimal change disease

MCP

Monocyte/macrophage chemoattractant protein

MCP-1

Monocyte chemoattractant protein 1

MCS

Multi-species conserved sequence

M-CSF

Macrophage colony-stimulating factor

MDM2

Mouse double minute 2

MDP

Muramyl dipeptide

MDR

Multidrug resistance (gene)

MedDRA

Medical Dictionary for Regulatory Activities Terminology

MEF2A

Myocyte-enhancing factor 2A

Megsin

Mesangial cell-specific gene with homology to serpin

MEN

Multiple endocrine neoplasm

MeSH

Medical Subject Headings

MeV

Multiexperiment viewer

MGED

Microarray Gene Expression Data society

MGMT

O6-Methylguanine-DNA methyltransferase

MHC

Major histocompatability complex

MI

Myocardial infarction

MIAME

Minimal Information About a Microarray Experiment

MIM

Metastasis-inclined microenvironment

miR-192

MicroRNA-192

miRNA

Micro-ribonucleic acid

MITF

Microphthalmia transcription factor

MLEM

Maximum likelihood expectation maximization

MLPA

Multiplex ligation-dependent probe amplification

MMP

Matrix metalloproteinase

MMP-3

Matrix metalloproteinase-3

MMR

Mismatch repair

MPSS

Massively parallel signature sequencing

MPTP

1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine

mQTL

Metabolite quantitative trait loci

mRNA

Messenger ribonucleic acid

mRSS

Modified Rodnan Skin Score

MS

Multiple sclerosis

MS

Multispectral

MS/MS

Tandem mass spectrometry

MSA

Multiple system atrophy

MTDNA

Mitochondrial DNA

MTHFR

Methylenetetrahydrofolate reductase (gene)

mTOR

Mammalian target of rapamycin

MTP

Microsomal triglyceride transfer protein

MTX

Methotrexate

MudPIT

Multidimensional protein identification technology

MVP

Mitral valve prolapse

MZ

Monozygotic

NAAT

Nucleic acid amplification testing

NAD(P)H

Nicotinamide adenine dinucleotide phosphate reduced form

NAFLD

Non-alcoholic fatty liver disease

NASH

Non-alcoholic steatohepatitis

NAT2

N-Acetyltransferase 2

NAWM

Normal appearing white matter

NC

Nucleocapsid (viral protein)

N-CAM

Neural cell adhesion molecule

NCBI

National Center for Biotechnology Information

NCE

New chemical entity

NCEP

National Cholesterol Education Program

NCI60

Refers to a set of 60 cancer cell lines curated at the NCI (National Cancer Institute)

ncRNA

Non-coding RNA

NEF

NEgative regulatory Factor (viral protein)

NER

Nucleotide excision repair

NF1/2

Neurofibromatosis1/2

NHGRI

National Human Genome Research Institute

NHR

Non-homologous recombination

NIEHS

National Institute of Environmental Health Sciences (NIH)

NIH

National Institutes of Health

NK

Natural killer

NMR

Nuclear magnetic resonance

NNRTI

Non-nucleosidic reverse transcriptase inhibitor

NOD

Nucleotide oligomerization domain (gene)

NPV

Negative predictive value

NQO1

Nicotinamide adenine dinucleotide phosphate oxidoreductase

NRTI

Nucleosidic reverse transcriptase inhibitor

NSAID

Non-steroidal anti-inflammatory drug

nt

Nucleotides

NUD

Non-ulcer dyspepsia

NYHA

New York Heart Association

OBO

Open Biomedical Ontologies

OCTN

Organic cation transporter (gene)

OHCA

Out of hospital cardiac arrest

OMIM

Online Mendelian Inheritance in Man

OMP

Outer membrane protein

OmpC

Outer membrane porin C of E. coli

opn

Osteopontin (gene)

OPN

Osteopontin (protein)

OR

odds ratio

ORESTES

Open reading frame expressed sequence tags

ORF

Open reading frame

OSEM

Ordered subset expectation maximization

p53BP1

p53 Binding protein 1

PAD

Peripheral arterial disease

PAGE

Polyacrylamide gel electrophoresis

PAI

Pathogenicity island

PAM

Prediction analysis of microarrays

pANCA

Perinuclear antineutrophil cytoplasmatic antibodies

PAOD1

Peripheral arterial occlusive disease

Pap

Papanicolaou

Parvo B19

Human parvovirus B-19

PBC

Primary biliary cirrhosis

PBL

Peripheral blood lymphocytes

PBMC

Peripheral blood mononuclear cell

PC

Pyruvate carboxylase

PCA

Principal components analysis

PCNA

Proliferating cell nuclear antigen

PCR

Polymerase chain reaction

PCSK9

Proprotein convertase subtilisin/kexin type 9

PCV

Procarbazine/CCNU/vincristine

PD

Parkinson disease

PD

Pharmacodynamic

PDA

Patent ductus arteriosus

PDA

Personal digital assistant

PDD

Parkinson disease with dementia

PDGF

Platelet-derived growth factor

PDGFR

Platelet-derived growth factor receptor

PDH

Pyruvate dehydrogenase

PDTC

Pyrrolidine dithiocarbamate

PDYN

prodynorphin (gene)

PFGE

Pulse field gel electrophoresis

PGE2

Prostaglandin E2

PGx

Pharmacogenetics and pharmacogenomics

PHT

Phenytoin

PI

Protease inhibitor

PI3K

Phosphotidylinositol triphosphate kinase

PIN

Prostatic intraepithelial neoplasia

PK

Pharmacokinetics

PLTP

Phospholipid transfer protein

PMAGE

Polony Multiplex Analysis of Gene Expression

PMBC

Peripheral blood mononuclear cells

PML-RAR

Pro-myelocytic leukemia retinoic acid receptor oncoprotein

PON1

Paraoxonase

PPI

Percutaneous peripheral intervention

PPV

Positive predictive value

PR

Protease (viral)

PrEC

Prostate epithelial cells

PRIDE

Proteomics Identifications Database

PRNP

Prion protein (gene)

PS

Pulmonary stenosis

PSA

Prostate-specific antigen

PsA

Psoriatic arthritis

PSC

Primary sclerosing cholangitis

PSP

Progressive supranuclear palsy

PTEN

Phosphatase and tensin homolog

PTM

Pre-trans-splicing molecule

PUD

Peptic ulcer disease

PZ

Plasticity zone

QPCR

Quantitative PCR

qRT

Quantitative real-time PCR

qRT-PCR

Quantitative reverse-transcriptase polymerase chain reaction

QTL

Quantitative trait locus

QT-PCR

Quantitative real-time polymerase chain reaction

QV

Quality value

R&D

Research and Development

RA

Rheumatoid arthritis

RAAS

Renin-angiotensin-aldosterone system

RAPD-PCR

Random amplified polymorphic deoxyribonucleic acid–polymerase chain reaction

RB

Retinoblastoma

RB

Retinoblastoma (gene)

RCM

Restrictive cardiomyopathy

REPAIR-AMI

Reinfusion of enriched progenitor cells and infarct remodeling in acute myocardial infarction

RET

Ret proto-oncogene

REV

REgulator of Virion protein expression (viral protein)

RFLP

Restriction fragment length polymorphism

RISC

RNA interference silencing complex

RNA

Ribonucleic acid

RNAi

Ribonucleic acid interference

ROC

RAS in complex proteins

ROCO

ROC (RAS of complex proteins)/COR (C-terminal of ROC)

ROS

Reactive oxygen species

RP

Rapid progression

RPA

Ribonuclease protection assay

RSV

Respiratory syncytial virus

RT

Reverse transcriptase (viral protein)

RT-PCR

Real-time polymerase chain reaction

RT-PCR

Reverse transcription – polymerase chain reaction

RV