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DNA Biomarkers for Pharmacogenomics and Personalized Medicine

  • John Raelson*
  • Abdelmajid Belouchi
Chapter

Abstract

Genome-wide association studies are expected to soon provide a significant increase in disease associated DNA sequences that can serve as biomarkers for diagnosis and treatment for psychiatric illnesses. These biomarkers have the potential to identify precisely defined disease phenotypes and to predict effective individually specific therapies. This chapter reviews the current knowledge of the association between DNA markers and disease phenotypes and discusses some of the anticipated problems that need to be overcome before DNA biomarkers can provide specific and sensitive diagnostic tests for both the presence of disease and the prediction of individual response to specific drugs.

Keywords

Attention Deficit Hyperactivity Disorder Bipolar Disorder Major Depression Disorder Generalize Anxiety Disorder Single Nucleotide Polymorphism Marker 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

Abbreviations

ADHD

Attention deficit hyperactivity disorder

ADME

Genes, genes whose products are involved in absorption, distribution, metabolism and excretion of drugs

BPD

Bipolar disorder

CATIE

Clinical Antipsychotic Trials of Intervention Effectiveness

χ2

Chi-square statistic for significance of counts

DNA

Deoxyribonucleic acid

FDA

Food and Drug Administration USA

GAD

Generalized anxiety disorder

GAIN

Genetic Association Information Network

GWAS

Genome-wide association study(ies) (=WGAS)

LD

Linkage disequilibrium

MDD

Major depressive disorder

NIH

National Institute of Health USA

NPV

Negative predictive value of a diagnostic test

PPV

Positive predictive value of a diagnostic test

Pr

Prevalence of a disease or phenotype in a population

RNA

Ribonucleic acid

Se

Sensitivity of a diagnostic test

SNP

Single nucleotide polymorphism

Sp

Specificity of a diagnostic test

STAR*D

Sequenced Treatment Alternatives for Depression Study

SZ

Schizophrenia

WGAS

Whole genome association study(ies) (=GWAS)

WTCCC

Wellcome Trust Case-Control Consortium

Gene Abbreviations

ABCB1

Adenosine tri-phosphate-binding cassette sub-family B member 1, chromosome 7q21.12

ADH1A

Class I alcohol dehydrogenase 1 alpha subunit, chromosome 4q23

ADH1B

Class I alcohol dehydrogenase 1 beta subunit, chromosome 4q23

ADH4

Class II alcohol dehydrogenase 4 pi subunit, chromosome 4q23

ALDH2

Mitochondrial aldehyde dehydrogenase 2, chromosome 12q24.12

AOX

Aldehyde oxidase, chromosome 2p33.1

BDNF

Brain derived neurotrophic factor, chromosome 11p14.1

BRCA1

Breast cancer 1, chromosome 17q21.311

CARD15 (=NOD2)

Caspase recruitment domain 15 gene, chromosome 16q12.1

CHRM2

Cholinergic receptor muscarinic 2, chromosome 7q33

COMT

Catechol-O-methyltransferase, chromosome 22q11.21

CYP (=P450)

Cytochrome heme protein with pigment at 450 nm absorption; very large family of heme containing proteins involved in multi-component electron transfer chains. Many are involved in drug metabolism.

CYP2E1

Cytochrome P450, family 2, subfamily E, polypeptide 1 variant, chromosome 10q26.3

DAO

d-amino acid oxidase, chromosome 12q24.11

DAT1 (SLC6A3)

Dopamine transporter, (=solute carrier family 6) chromosome 5p15.33

DBH

Dopamine β-hydroxylase precursor, chromosome 9q34.2

DISC1

Disrupted in schizophrenia 1, chromosome 1q42.2

DRD1

Dopamine receptor D1, chromosome 5q35.2

DRD2

Dopamine receptor D2, chromosome 11q23.1-q23.2

DRD3

Dopamine receptor D3, chromosome 3q13.31

DRD4

Dopamine receptor D4, chromosome 11p15.5

DRD5

Dopamine receptor D5, chromosome 4p16.1

DTNBP1

Distrobrevin binding protein 1, (=dysbindin), chromosome 6p22.3)

ERRB4 (=HER4)

The genomic homologue of erythroblastic leukemia viral oncogene, chromosome 2q34)

FMO3

Flavin containing mono-oxygenase 3 isoform, chromosome 1q24.3

GABRA2

Gamma aminobutyric acid A receptor, chromosome 4p12

GAD2

Glutamate decarboxylase 2, chromosome 10p12.1

HTR1B

5-Hydroxy tryptamine (serotonin) receptor 1B, chromosome 6q14

HTR2A

5-Hydroxy tryptamine (serotonin) receptor 2A, chromosome 13q14.2

5-HTT (=SLC6A4, =hSERT)

5-Hydroxy tryptamine transporter = serotonin symporter), chromosome 17q11.1-q12

5-HTTLPR

5-HTT linked polymorphic region, a repeat length polymorphism in the promoter of the serotonin transporter gene

LG72 (=G72 = DAOA)

d-amino acid oxidase activator, chromosome 13q33.2

MAOA

Monoamine oxidase A, chromosome Xp11.3

NOD2 (=CARD15)

Nucleotide binding oligomerization domain, chromosome 16q12.1

NRG1

Neuregulin 1, chromosome 8p12

PI3K/AKT

Phosphatidylinositol 3-kinase-AKT protein substrate, cell signaling pathway, multiple genes

PPARG

Peroxisome proliferative activator receptor gamma, chromosome 3p25.2-p25.1

SLC6A4 (=5-HTT = hSERT)

Solute carrier family 6 neurotransmitter transporter (=5- hydroxy tryptamine transporter = serotonin symporter), chromosome 17q11.1-q12

SNAP25

Synaptosome associated protein, chromosome 20p12.2

TAS2R16

Taste receptor 16, chromosome 7q31.32

TPH1

Tryptophan hydroxylase 1, chromosome 11p15.1

UGT1A4

Uridine di-phosphate glycosyltransferase 1 family, polypeptide A4, chromosome 2q37.1

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Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • John Raelson*
    • 1
  • Abdelmajid Belouchi
  1. 1.Genizon BiosciencesMcCaffreyCanada QCH4T 2C7

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