Fundamentals

3. Pharmacology of Human Drug Response 53

Pharmacology and genetics of human drug response are complementary 53

Dose-response relationships 54

Pharmacokinetics in pharmacogenetics 60

Pharmacogenetic mechanisms of human drug response 64

Testing pharmacogenetic hypotheses 64

Summary 70

4. Age-Related Pharmacology 72

Age-related physiological variation 73

Pharmacokinetic variation 74

Pharmacodynamic variation 89

Summary 95

5. Genetics in Pharmacology 99

The fine structure of genetic profiling human drug response 99

Some elementary features of the human genome 101 Framework for dissecting genetic variation in human drug response 104

Twin studies 105

Inheritance patterns of monogenic traits 110

Mathematical treatment of heterogeneity in human drug response 116

Molecular pharmacogenetics 130

Impediments to pharmacogenetic investigation 134

Summary 137

6. Epigenetics 142

The emergence of epigenetics 143

The foundations of epigenetics 145

The effect of molecular biology on epigenetics 148

Epigenetics in health and disease 159

Therapeutic potential for epigenetic disease 172

Summary 176

7. Genomic Tools 184

Charting the evolution of genomic tools 185

Conventional analytical techniques 188

Conventional analysis of genetic variants 189

Advances in genomic technology 199

Emerging technologies 211

Summary 218

8. Ethnic Pharmacogenetics 231

Marrying race and ethnicity to genetic variation 231

Grappling with race and ethnicity during the twentieth century 232

Ethnic specificity in drug response 236

Frequency of pharmacogenetic ethnic specificities 237 Ethnicity as a starting point for pharmacogenetic investigation 245

Ethnic specificity in drug development 249

Culturally specific risks of ethnic research 249

Summary 252

9. Modeling Human Drug Response 258

Mouse models of pharmacogenetic traits 259

Constructing inbred mouse models 260 Mouse models of the arylhydrocarbon receptor and N-acetyltransferase polymorphisms 269

Creating mouse models by gene targeting 276

Mouse models of human disorders created by gene targeting 279

Quantitative trait locus (QTL) analysis 279

Modeling with simple eukaryotic organisms 289

Summary 290

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