Introduction 1

Overview of Genetics 1

1.1 A Look Ahead 2

1.2 From Genes to Genomes 6
DNA 6
Gene 6
Chromosome 6
Genome 6
Cells, Tissues, and Organs 6
Individual 7
Family 7
Population 7
Evolution 7

1.3 Genes Do Not Usually Function Alone 7

1.4 Geneticists Use Statistics to Represent Risks 9

1.5 Applications of Genetics 10
Establishing Identity - From Forensics to Rewriting History 11
Health Care 11
Agriculture 12
A Word on Genetic Equity 14

Chapter 2

Cells 19

2.1 The Components of Cells 20
Chemical Constituents of Cells 21
Organelles 21
The Cell Membrane 26
The Cytoskeleton 28

2.2 Cell Division and Death 32
The Cell Cycle 32
Apoptosis 35

2.3 Cell-Cell Interactions 36
Signal Transduction 36
Cellular Adhesion 37

2.4 Stem Cells and Cell Specialization 38

2.5 Viruses and Prions - Not Cells, But Infectious 40
A Virus - Nucleic Acid in a Protein Coat 40
A Prion - One Protein That Takes Multiple Forms 41

Chapter 3

Development 47

3.1 The Reproductive System 48
The Male 48
The Female 48

3.2 Meiosis 49

3.3 Gamete Maturation 53
Sperm Development 53
Oocyte Development 55

3.4 Prenatal Development 56
Fertilization 56
Early Events - Cleavage and Implantation 57
The Embryo Forms 59
Supportive Structures 59
On the Matter of Multiples 59
The Embryo Develops 62
The Fetus 63

3.5 Birth Defects 64
The Critical Period 64
Teratogens 65

3.6 Maturation and Aging 67
Adult-Onset Inherited Disorders 67
Accelerated Aging Disorders 69
Is Longevity Inherited? 69

Part Two

Transmission Genetics 75

Chapter 4

Mendelian Inheritance 75

4.1 Following the Inheritance of One Gene - Segregation 76
Mendel the Man 76
Mendel's Experiments 76
Terms and Tools to Follow Segregating Genes 79

4.2 Single Gene Inheritance in Humans 80
Modes of Inheritance 80
On the Meaning of Dominance and Recessiveness 84

4.3 Following the Inheritance of Two Genes - Independent Assortment 85

4.4 Pedigree Analysis 87
Pedigrees Then and Now 87
Pedigrees Display Mendel's Laws 89

Chapter 5

Extensions and Exceptions to Mendel's Laws 95

5.1 When Gene Expression Appears to Alter Mendelian Ratios 96
Lethal Allele Combinations 96
Multiple Alleles 96
Different Dominance Relationships 97
Epistasis - When One Gene Affects Expression of Another 98
Penetrance and Expressivity 99
Pleiotropy - One Gene, Many Effects 100
Phenocopies - When It's Not in the Genes 102
Genetic Heterogeneity - More than One Way to Inherit a Trait 102

5.2 Maternal Inheritance and Mitochondrial Genes 103
Mitochondrial Disorders 104
Heteroplasmy Complicates Mitochondrial Inheritance 105
Mitochondrial DNA Studies Clarify the Past 105

5.3 Linkage 106
Linkage Was Discovered in Pea Plants 106
Linkage Maps 107
Examples of Linked Genes in Humans 108
The Evolution of Gene Mapping 109

Chapter 6

Matters of Sex 115

6.1 Sexual Development 116
Sex Chromosomes 116
The Phenotype Forms 117
Gender Identity - Is Homosexuality Inherited? 119

6.2 Traits Inherited on Sex Chromosomes 120
X-Linked Recessive Inheritance 120
X-Linked Dominant Inheritance 125

6.3 X Inactivation Equalizes the Sexes 126

6.4 Gender Effects on Phenotype 128
Sex-limited Traits 129
Sex-influenced Traits 129
Genomic Imprinting 129

Multifactorial Traits 137

7.1 Genes and the Environment Mold Most Traits 138
Polygenic Traits Are Continuously Varying 139
Fingerprint Patterns, Height, and Eye Color 139
A Closer Look at Skin Color 140

7.2 Methods Used to Investigate Multifactorial Traits 142
Empiric Risk 142
Heritability - The Genetic Contribution to a Multifactorial Trait 144
Adopted Individuals 145
Twins 145
Association Studies 147

7.3 Some Multifactorial Traits 149
Heart Health 149
Body Weight 151

The Genetics of Behavior 155

8.1 Genes Contribute to Most Behavioral Traits 156

8.2 Eating Disorders 158

8.3 Sleep 159

8.4 Intelligence 160

8.5 Drug Addiction 161

8.6 Mood Disorders 163

8.7 Schizophrenia 164

DNA and Chromosomes 171

DNA Structure and Replication 171

9.1 Experiments Identify and Describe the Genetic Material 172
DNA Is the Hereditary Molecule 172
DNA Is the Hereditary Molecule - and Protein Is Not 172
Deciphering the Structure of DNA 174

9.2 DNA Structure 176

9.3 DNA Replication - Maintaining Genetic Information 178
Replication Is Semiconservative 178
Steps and Participants in DNA Replication 180

9.4 PCR - Directing DNA Replication 183

Gene Action and Expression 189

10.1 Transcription - The Link Between Gene and Protein 190
RNA Structure and Types 190
Transcription Factors 192
Steps of Transcription 193
RNA Processing 194

10.2 Translating a Protein 196
Deciphering the Genetic Code 196
Building a Protein 199
Protein Folding 201

10.3 The Human Genome Sequence Reveals Unexpected Complexity 203
Genome Economy: Reconciling Gene and Protein Number 204
What Does the Other 98.5 Percent of the Human Genome Do? 206

Gene Mutation 211

11.1 Mutations Can Alter Proteins - Three Examples 212
The Beta Globin Gene 212
Disorders of Orderly Collagen 214
A Mutation That Causes Early-Onset Alzheimer Disease 215

11.2 Causes of Mutation 216
Spontaneous Mutation 216
Induced Mutations 218
Natural Exposure to Mutagens 219

11.3 Types of Mutations 220
Point Mutations 220
Deletions and Insertions Can Cause Frameshifts 221
Pseudogenes and Transposons Revisited 222
Expanding Repeats Lead to Protein Misfolding 222

11.4 The Importance of a Mutation's Position in the Gene 225
Globin Variants 225
Inherited Susceptibility to Prion Disorders 226

11.5 Factors That Lessen the Effects of Mutation 227

11.6 DNA Repair 227
Types of DNA Repair 227
DNA Repair Disorders 228

Chromosomes 235

12.1 Portrait of a Chromosome 236
Telomeres and Centromeres Are Essential 237
Karyotypes Are Chromosome Charts 238

12.2 Visualizing Chromosomes 240
Obtaining Cells for Chromosome Study 240
Preparing Cells for Chromosome Observation 243

12.3 Abnormal Chromosome Number 246
Polyploidy 246
Aneuploidy 246

12.4 Abnormal Chromosome Structure 252
Deletions and Duplications 252
Translocations 253
Inversions 256
Isochromosomes and Ring Chromosomes 258

12.5 Uniparental Disomy - Two Genetic Contributions from One Parent 259

Population Genetics 263

When Allele Frequencies Stay Constant 263

13.1 The Importance of Knowing Allele Frequencies 264

13.2 When Allele Frequencies Stay Constant - Hardy-Weinberg Equilibrium 264

13.3 Practical Applications of Hardy-Weinberg Equilibrium 267

13.4 DNA Fingerprinting - A Practical Test of Hardy-Weinberg Assumptions 268
DNA Patterns Distinguish Individuals 269
Population Statistics Are Used to Interpret DNA Fingerprints 269
DNA Fingerprinting to Identify World Trade Center Victims 272

Changing Allele Frequencies 277

14.1 Nonrandom Mating 278

14.2 Migration 279
Historical Clues 279
Geographical and Linguistic Clues 279

14.3 Genetic Drift 280
The Founder Effect 280
Population Bottlenecks 282

14.4 Mutation 284

14.5 Natural Selection 284
Tuberculosis Ups and Downs - and Ups 284
Evolving HIV 285
Balanced Polymorphism 286

14.6 Gene Genealogy 292
PKU Revisited 292
CF Revisited 293

Human Origins and Evolution 299

15.1 Human Origins 300
The Australopithecines - And Others? 301
Homo 303
Modern Humans 304

15.2 Molecular Evolution 305
Comparing Genomes 305
Comparing Chromosomes 306
Comparing Protein Sequences 307
Comparing DNA Sequences 310

15.3 Molecular Clocks 313
Neanderthals Revisited 313
Choosing Clues 313

15.4 Eugenics 316

Immunity and Cancer 323

Genetics of Immunity 323

16.1 The Importance of Cell Surfaces 324
Blood Groups 324
The Human Leukocyte Antigens 326

16.2 The Human Immune System 327
Physical Barriers and the Innate Immune Response 327
The Adaptive (Acquired) Immune Response 329

16.3 Abnormal Immunity 334 Inherited Immune Deficiencies 334
Acquired Immune Deficiency Syndrome 334
Autoimmunity 336
Allergies 338

16.4 Altering Immune Function 339
Vaccines 339
Immunotherapy 341
Transplantation 342

16.5 A Genomic View of Immunity - The Pathogen's Perspective 344
Crowd Diseases 345
Bioweapons 345

The Genetics of Cancer 351

17.1 Cancer as a Genetic Disorder 352
Cancer in Families 352
Loss of Cell Cycle Control 353
Inherited Versus Sporadic Cancer 354

17.2 Characteristics of Cancer Cells 354

17.3 Genes That Cause Cancer 356
Oncogenes 356
Tumor Suppressors 358

17.4 A Series of Genetic Changes Causes Some Cancers 363
A Rapidly Growing Brain Tumor 363
Colon Cancer 363

17.5 Cancer Prevention, Diagnosis, and Treatment 364
Diet-Cancer Associations 364
Diagnosing and Treating Cancer 365

Genetic Technology 371

Genetically Modified Organisms 371

18.1 Of Pigs and Patents 372

18.2 Recombinant DNA Technology 373
Constructing Recombinant DNA Molecules 374
Selecting Recombinant DNA Molecules 376
Isolating the Gene of Interest 376
Applications of Recombinant DNA Technology 377

18.3 Transgenic Organisms 378
Delivering DNA 378
Transgenic Pharming from Milk and Semen 379

18.4 Gene Targeting 382
Gene-Targeted Mice as Models 383
When Knockouts Are Normal 385

Gene Therapy and Genetic Counseling 389

19.1 Gene Therapy Successes and Setbacks 390
Adenosine Deaminase Deficiency - Early Success 390
Ornithine Transcarbamylase Deficiency - A Setback 392
A Success in the Making - Canavan Disease 393

19.2 The Mechanics of Gene Therapy 394
Treating the Phenotype 394
Germline Versus Somatic Gene Therapy 395
Sites of Somatic Gene Therapy 395
Gene Delivery 398

19.3 A Closer Look: Treating Sickle Cell Disease 399

19.4 Genetic Screening and Genetic Counseling 401
Genetic Counselors Provide Diverse Services 401
Scene from a Sickle Cell Disease Clinic 403
Genetic Counseling Quandaries and Challenges 403
Perspective: A Slow Start, But Great Promise 403

Agricultural Biotechnology 407

20.1 Traditional Breeding Compared to Biotechnology 409
Similar Steps, Different Degree of Precision 409
Government Regulation of Crops 411
Biotechnology Provides Different Routes to Solving a Problem 411

20.2 Types of Plant Manipulations 412
Altering Plants at the Gene Level 412
Altering Plants at the Cellular Level 415

20.3 Release of Genetically Modified Organisms into the Environment 417
Microcosm Experiments 417
Field Tests 417
Bioremediation 418

20.4 Economic, Ecological, and Evolutionary Concerns 418

20.5 The Impact of Genomics 420

Reproductive Technologies 425

21.1 New Ways to Make Babies 426
Grandmother and Mother at the Same Time 426
Midlife Motherhood 426
A Five-Year Wait 426

21.2 Infertility and Subfertility 427
Male Infertility 427
Female Infertility 428
Infertility Tests 430

21.3 Assisted Reproductive Technologies 430
Donated Sperm - Artificial Insemination 430
A Donated Uterus - Surrogate Motherhood 431
In Vitro Fertilization 432
Gamete Intrafallopian Transfer 432
Oocyte Banking and Donation 433
Preimplantation Genetic Screening and Diagnosis 433

21.4 On the Subject of "Spares" 435

The Human Genome Project and Genomics 441

22.1 Genome Sequencing: A Continuation of Genetics 442

22.2 The Origin of the Idea 446 The Sanger Method of DNA Sequencing 446
The Project Starts 448

22.3 Technology Drives the Sequencing Effort 448

22.4 Genome Information Answers and Raises Questions 450
The Definition of a Gene 450
Nonhuman Genome Projects 450
Epilogue: Genome Information Will Affect You 452