Language: English
Pages: 448
Contents......Page 12
I. FOUNDATIONS......Page 16
1. Beginnings......Page 18
Cellular foundations of early pharmacology and genetics......Page 19
Molecular foundations of early pharmacology and genetics......Page 20
Emergence of modern genetics and experimental pharmacogenetics......Page 23
Informational foundations of modern genetics......Page 25
The effect of molecular biology on pharmacogenetics......Page 28
2. Defining Pharmacogenetics......Page 33
The genetic profile of human drug response......Page 34
Evidence for individual variation in drug response......Page 39
Evidence that variation in drug response is inherited......Page 40
The scope of pharmacogenetics......Page 42
Strategies for gene identification......Page 52
Linking pharmacogenetics to clinical applications......Page 60
Summary......Page 63
II. FUNDAMENTALS......Page 66
Pharmacology and genetics of human drug response are complementary......Page 68
Dose–response relationships......Page 69
Pharmacokinetics in pharmacogenetics......Page 75
Testing pharmacogenetic hypotheses......Page 79
Summary......Page 85
4. Age-Related Pharmacology......Page 87
Age-related physiological variation......Page 88
Pharmacokinetic variation......Page 89
Pharmacodynamic variation......Page 104
Summary......Page 110
The fine structure of genetic profiling human drug response......Page 114
Some elementary features of the human genome......Page 116
Framework for dissecting genetic variation in human drug response......Page 119
Twin studies......Page 120
Inheritance patterns of monogenic traits......Page 125
Mathematical treatment of heterogeneity in human drug response......Page 131
Molecular pharmacogenetics......Page 145
Impediments to pharmacogenetic investigation......Page 149
Summary......Page 152
6. Epigenetics......Page 157
The emergence of epigenetics......Page 158
The foundations of epigenetics......Page 160
The effect of molecular biology on epigenetics......Page 163
Epigenetics in health and disease......Page 174
Therapeutic potential for epigenetic disease......Page 187
Summary......Page 191
7. Genomic Tools......Page 199
Charting the evolution of genomic tools......Page 200
Conventional analytical techniques......Page 203
Conventional analysis of genetic variants......Page 204
Advances in genomic technology......Page 214
Emerging technologies......Page 226
Summary......Page 233
Marrying race and ethnicity to genetic variation......Page 246
Grappling with race and ethnicity during the twentieth century......Page 247
Ethnic specificity in drug response......Page 251
Frequency of pharmacogenetic ethnic specificities......Page 252
Ethnicity as a starting point for pharmacogenetic investigation......Page 260
Culturally specific risks of ethnic research......Page 264
Summary......Page 266
9. Modeling Human Drug Response......Page 273
Mouse models of pharmacogenetic traits......Page 274
Constructing inbred mouse models......Page 275
Mouse models of the arylhydrocarbon receptor and N-acetyltransferase polymorphisms......Page 284
Creating mouse models by gene targeting......Page 291
Quantitative trait locus (QTL) analysis......Page 294
Modeling with simple eukaryotic organisms......Page 304
Summary......Page 305
III. FUTURES......Page 310
Changing pharmaceutical perspectives......Page 312
Human drug efficacy targets......Page 314
Small molecule drug discovery......Page 317
Protein therapeutics......Page 323
Genetic pathways to improved drug therapy......Page 338
Summary......Page 349
11. Predictive Biology......Page 353
Indexing pharmacogenetic knowledge......Page 354
Edging toward personalized medicine......Page 355
Digging deeper into human genetic variation......Page 374
New dimensions in drug discovery......Page 385
When good drugs go bad, what to do?......Page 392
Summary......Page 394
Synthesis......Page 404
Appendix A......Page 408
Appendix B......Page 427
Appendix C......Page 429
A......Page 432
C......Page 433
D......Page 435
E......Page 437
G......Page 438
H......Page 440
M......Page 441
P......Page 443
R......Page 445
S......Page 446
U......Page 447
Z......Page 448
