Essential Genetics and Genomics

Essential Genetics and Genomics......Page 3
Copyright......Page 4
Brief Contents......Page 5
Contents......Page 6
Preface......Page 17
The Student Experience......Page 22
Readiness Assessment and Readiness Review......Page 26
Acknowledgments......Page 27
About the Author......Page 29
For the Student......Page 30
Chapter 1 The Genetic Code of Genes and Genomes......Page 33
1.1 DNA is the molecule of heredity......Page 34
Genetic traits can be altered by treatment with pure DNA......Page 35
Transmission of DNA is the link between generations......Page 36
A central feature of double-stranded DNA is complementary base pairing......Page 39
In replication, each parental DNA strand directs the synthesis of a new partner strand......Page 40
Enzyme defects result in inborn errors of metabolism......Page 41
Genetic analysis led to the one gene–one enzyme hypothesis......Page 44
the human connection One Gene, One Enzyme......Page 45
Mutant screens sometimes isolate different mutations in the same gene......Page 48
A complementation test identifies mutations in the same gene......Page 49
One of the DNA strands directs the synthesis of a molecule of RNA......Page 52
A molecule of RNA directs the synthesis of a polypeptide chain......Page 54
The genetic code is a triplet code......Page 55
1.5 Genes change by mutation......Page 56
Groups of related organisms descend from a common ancestor......Page 58
The molecular unity of life is seen in comparisons of genomes......Page 59
Chapter 2 Transmission Genetics: Heritage from Mendel......Page 65
Mendel was careful in his choice of traits......Page 66
Reciprocal crosses yield the same types of offspring......Page 67
The wrinkled mutation causes an inborn error in starch synthesis......Page 68
2.2 Genes come in pairs, separate in gametes, and join randomly in fertilization......Page 71
Genes are physical entities that come in pairs......Page 72
Gametes unite at random in fertilization......Page 73
The progeny of the F2 generation support Mendel’s hypothesis......Page 74
The progeny of testcrosses also support Mendel’s hypothesis......Page 75
The F2 genotypes in a dihybrid cross conform to Mendel’s prediction......Page 77
The progeny of testcrosses show the result of independent assortment......Page 80
The multiplication rule applies to independent possibilities......Page 81
2.5 The results of segregation can be observed in human pedigrees......Page 83
Most differences in human genes are not harmful......Page 85
2.6 Simple dominance is not always observed......Page 86
The human ABO blood groups illustrate both dominance and codominance......Page 88
A mutant gene can affect more than one trait......Page 90
2.7 Epistasis can affect the observed ratios of phenotypes......Page 91
the human connection Blood Feud......Page 94
Chapter 3 The Chromosomal Basis of Heredity......Page 101
3.1 Each species has a characteristic set of chromosomes......Page 102
3.2 The daughter cells of mitosis have identical chromosomes......Page 103
In mitosis, the replicated chromosomes align on the spindle, and the sister chromatids pull apart......Page 104
3.3 Meiosis results in gametes that differ genetically......Page 106
The first meiotic division reduces the chromosome number by half......Page 107
The nucleosome is the basic structural unit of chromatin......Page 114
Chromatin fibers form discrete chromosome territories in the nucleus......Page 115
The metaphase chromosome is a hierarchy of coiled coils......Page 117
Heterochromatin is rich in satellite DNA and low in gene content......Page 119
The telomere is essential for the stability of the chromosome tips......Page 120
Telomere length limits the number of cell doublings......Page 122
Special chromosomes determine sex in many organisms......Page 123
Hemophilia is a classic example of human X-linked inheritance......Page 124
Experimental proof of the chromosome theory came from nondisjunction......Page 126
3.7 Genetic data analysis makes use of probability and statistics......Page 128
Progeny of crosses are predicted by the binomial probability formula......Page 129
Chi-square tests goodness of fit of observed to expected numbers......Page 131
Chapter 4 Gene Linkage and Genetic Mapping......Page 141
4.1 Linked alleles tend to stay together in meiosis......Page 142
The degree of linkage is measured by the frequency of recombination......Page 143
The frequency of recombination differs from one gene pair to the next......Page 144
Recombination does not occur in Drosophila males......Page 145
4.2 Recombination results from crossing-over between linked alleles......Page 146
Physical distance is often—but not always—correlated with map distance......Page 150
One crossover can undo the effects of another......Page 152
4.3 Double crossovers are revealed in three-point crosses......Page 154
Interference decreases the chance of multiple crossing-over......Page 157
Single-nucleotide polymorphisms (SNPs) are abundant in the human genome......Page 158
Gene dosage can differ owing to copy-number variation (CNV)......Page 159
Short tandem repeats (STRs) often differ in copy number......Page 160
the human connection Starch Contrast......Page 162
4.5 Tetrads contain all four products of meiosis......Page 163
Tetrad analysis affords a convenient test for linkage......Page 164
The geometry of meiosis is revealed in ordered tetrads......Page 166
Gene conversion suggests a molecular mechanism of recombination......Page 168
4.6 Recombination is initiated by a double-stranded break in DNA......Page 170
Recombination tends to take place at preferred positions in the genome......Page 172
Chapter 5 Human Chromosomes and Chromosome Behavior......Page 179
The standard human karyotype consists of 22 pairs of autosomes and two sex chromosomes......Page 180
Chromosomes with no centromere, or with two centromeres, are genetically unstable......Page 181
Dosage compensation adjusts the activity of X-linked genes in females......Page 183
The calico cat shows visible evidence of X-chromosome inactivation......Page 185
The pseudoautosomal region of the X and Y chromosomes has gotten progressively shorter in evolutionary time......Page 186
The history of human populations can be traced through studies of the Y chromosome......Page 187
5.2 Chromosome abnormalities are frequent in spontaneous abortions......Page 189
Down syndrome results from three copies of chromosome 21......Page 190
An extra X or Y chromosome usually has a relatively mild effect......Page 191
The rate of nondisjunction can be increased by chemicals in the environment......Page 192
the human connection Catch 21......Page 193
A chromosome with a deletion has genes missing......Page 194
Rearrangements are apparent in giant polytene chromosomes......Page 195
A chromosome with a duplication has extra genes......Page 197
Human color-blindness mutations result from unequal crossing-over......Page 198
Some reciprocal deletions and duplications are associated with reciprocal risks of autism and schizophrenia......Page 199
A chromosome with an inversion has some genes in reverse order......Page 202
Reciprocal translocations interchange parts between nonhomologous chromosomes......Page 204
5.4 Polyploid species have multiple sets of chromosomes......Page 207
Polyploids can arise from genome duplications occurring before or after fertilization......Page 208
Polyploids can include genomes from different species......Page 210
5.5 The grass family illustrates the importance of polyploidy and chromosome rearrangements in genome evolution......Page 211
Chapter 6 DNA Structure, Replication, and Manipulation......Page 217
6.1 Genome size can differ tremendously, even among closely related organisms......Page 218
6.2 DNA is a linear polymer of four deoxyribonucleotides......Page 219
6.3 Duplex DNA is a double helix in which the bases form hydrogen bonds......Page 220
Nucleotides are added one at a time to the growing end of a DNA strand......Page 223
DNA replication is semiconservative: The parental strands remain intact......Page 224
DNA strands must unwind to be replicated......Page 227
6.5 Many proteins participate in DNA replication......Page 228
Each new DNA strand or fragment is initiated by a short RNA primer......Page 230
DNA polymerase has a proofreading function that corrects errors in replication......Page 231
One strand of replicating DNA is synthesized in pieces......Page 232
the human connection Sickle-Cell Anemia: The First “Molecular Disease”......Page 233
Single strands of DNA or RNA with complementary sequences can hybridize......Page 234
Restriction enzymes cleave duplex DNA at particular nucleotide sequences......Page 236
6.7 The polymerase chain reaction makes possible the amplification of a particular DNA fragment......Page 239
6.8 Chemical terminators and other methods are used to determine the base sequence......Page 241
The incorporation of a dideoxynucleotide terminates strand elongation......Page 242
Chapter 7 The Genetics of Bacteria and Their Viruses......Page 247
A plasmid is an accessory DNA molecule, often a circle......Page 248
Insertion sequences and transposons play a key role in bacterial populations......Page 249
Integrons have special site-specific recombinases for acquiring antibiotic-resistance cassettes......Page 251
Bacterial genomes can contain discrete regions of DNA from different sources......Page 254
7.2 Mutations that affect a cell’s ability to form colonies are often used in bacterial genetics......Page 255
7.3 Transformation results from the uptake of DNA and recombination......Page 256
7.4 In bacterial mating, DNA transfer is unidirectional......Page 257
Chromosome transfer begins at F and proceeds in one direction......Page 258
The unit of distance in the E. coli genetic map is the length of chromosomal DNA transferred in 1 minute......Page 260
7.5 Some phages can transfer small pieces of bacterial DNA......Page 262
the human connection The Sex Life of Bacteria......Page 264
7.6 Bacteriophage DNA molecules in the same cell can recombine......Page 267
Bacteriophages form plaques on a lawn of bacteria......Page 268
7.7 Lysogenic bacteriophages do not necessarily kill the host......Page 269
Specialized transducing phages carry a restricted set of bacterial genes......Page 271
Chapter 8 The Molecular Genetics of Gene Expression......Page 279
The proteins of humans and other vertebrates have a more complex domain structure than do the proteins of invertebrates......Page 280
8.3 The base sequence in DNA specifies the base sequence in an RNA transcript......Page 282
Eukaryotes have several types of RNA polymerase......Page 283
Promoter recognition typically requires multiple DNA-binding proteins......Page 284
RNA polymerase is a molecular machine for transcription......Page 286
Messenger RNA directs the synthesis of a polypeptide chain......Page 288
8.4 RNA processing converts the original RNA transcript into messenger RNA......Page 289
Splicing removes introns from the RNA transcript......Page 291
Human genes tend to be very long even though they encode proteins of modest size......Page 292
8.5 Translation into a polypeptide chain takes place on a ribosome......Page 293
Elongation takes place codon by codon......Page 294
A termination codon signals release of the finished polypeptide chain......Page 297
Most polypeptide chains fold correctly as they exit the ribosome......Page 298
Prokaryotes often encode multiple polypeptide chains in a single mRNA......Page 300
Genetic evidence for a triplet code came from three-base insertions and deletions......Page 301
Most of the codons were determined from in vitro polypeptide synthesis......Page 303
Redundancy and near-universality are principal features of the genetic code......Page 304
An aminoacyl-tRNA synthetase attaches an amino acid to its tRNA......Page 305
Much of the code’s redundancy comes from wobble in codon–anticodon pairing......Page 306
8.7 Several ribosomes can move in tandem along a messenger RNA......Page 307
Chapter 9 Molecular Mechanisms of Gene Regulation......Page 313
In positive regulation, the default state of transcription is “off.”......Page 314
Transcription sometimes occurs accidentally......Page 315
Lactose-utilizing enzymes can be inducible (regulated) or constitutive......Page 316
Repressor shuts off messenger RNA synthesis......Page 317
The lactose operon contains linked structural genes and regulatory sequences......Page 318
Stochastic noise aids induction of the lactose operon......Page 319
The lactose operon is also subject to positive regulation......Page 320
Tryptophan biosynthesis is regulated by the tryptophan operon......Page 321
Attenuation allows for fine-tuning of transcriptional regulation......Page 322
Riboswitches combine with small molecules to control transcriptional termination......Page 325
Galactose metabolism in yeast illustrates transcriptional regulation......Page 326
Transcription is stimulated by transcriptional activator proteins......Page 327
Enhancers increase transcription; silencers decrease transcription......Page 328
Genome architecture consists of compact domains of associating DNA molecules......Page 329
The eukaryotic transcription complex includes numerous protein factors......Page 331
Transcriptional inactivation is associated with heavy DNA methylation......Page 334
In mammals, some genes are imprinted by methylation in the germ line......Page 336
The coding capacity of the human genome is enlarged by extensive alternative splicing......Page 338
RNA interference results in the silencing of RNA transcripts......Page 339
the human connection Double Trouble......Page 340
9.7 Regulation can also take place at the level of translation......Page 342
Small regulatory RNAs can control translation by base-pairing with the messenger RNA......Page 343
Chapter 10 Genomics, Proteomics, and Genetic Engineering......Page 349
High-throughput DNA sequencing empowers personalized genomics......Page 350
A genome sequence without annotation is meaningless......Page 352
Comparison among genomes is an aid to annotation......Page 353
Ancient DNA indicates interbreeding between our ancestors and archaic human groups that became extinct......Page 355
Your genome sequence can help personalize your medical care......Page 356
the human connection Skeletons in Our Closet......Page 357
DNA microarrays and RNA-seq are used to estimate the relative level of gene expression of each gene in the genome......Page 358
Transcriptional profiling reveals groups of genes that are coordinately expressed during development......Page 360
Chromatin immunoprecipitation (ChIP) reveals protein–DNA interactions......Page 361
Yeast two-hybrid analysis reveals networks of protein interactions......Page 362
Restriction enzymes cleave DNA into fragments with defined ends......Page 365
A vector is a carrier for recombinant DNA......Page 367
A recombinant cDNA contains the coding sequence of a eukaryotic gene......Page 369
Loss of ß-galactosidase activity is often used to detect recombinant vectors......Page 371
10.4 CRISPR-Cas9 technology for gene editing has revolutionized genetic engineering......Page 373
CRISPR-Cas9 can be used to create knockout mutations of any gene......Page 374
CRISPR-Cas9 can be used to edit the sequence of any gene......Page 375
CRISPR-Cas9 can also be used in plants......Page 376
Animal growth rate can be genetically engineered......Page 377
Crop plants with improved nutritional qualities can be created......Page 378
The production of useful proteins is a primary impetus for recombinant DNA......Page 379
Chapter 11 The Genetic Control of Development......Page 385
Development in C. elegans exhibits a fixed pattern of cell divisions and cell lineages......Page 386
Developmental mutations often affect cell lineages......Page 387
Transmembrane receptors often mediate signaling between cells......Page 388
Cells can determine the fate of other cells through ligands that bind with their transmembrane receptors......Page 389
11.2 Epistatic interactions between mutant alleles can help define signaling pathways......Page 390
11.3 Development in Drosophila illustrates progressive regionalization and specification of cell fate......Page 393
Mutations in a maternal-effect gene result in defective oocytes......Page 394
Embryonic pattern formation is under genetic control......Page 395
the human connection Distinguished Lineages......Page 396
Coordinate genes establish the main body axes......Page 397
Gap genes regulate other genes in broad anterior–posterior regions......Page 398
Pair-rule genes are expressed in alternating segments or parasegments......Page 399
Homeotic genes function in the specification of segment identity......Page 400
Pax6 is a master regulator of eye development......Page 404
11.4 Floral development in Arabidopsis illustrates combinatorial control of gene expression......Page 405
Flower development in Arabidopsis is controlled by MADS box transcription factors......Page 406
Flower development in Arabidopsis is controlled by the combination of genes expressed in each concentric whorl......Page 407
Chapter 12 Molecular Mechanisms of Mutation and DNA Repair......Page 413
Germ-line mutations are inherited; somatic mutations are not......Page 414
Mutations can affect the amount or activity of the gene product, or the time or tissue specificity of expression......Page 415
Mutations in protein-coding regions can change an amino acid, truncate the protein, or shift the reading frame......Page 416
Sickle-cell anemia results from a missense mutation that confers resistance to malaria......Page 417
In the human genome, some trinucleotide repeats have high rates of mutation......Page 418
12.3 Transposable elements are agents of mutation......Page 421
Some transposable elements transpose via a DNA intermediate, others via an RNA intermediate......Page 422
Transposable elements can cause mutations by insertion or by recombination......Page 424
Almost 50 percent of the human genome consists of transposable elements, most of them no longer able to transpose......Page 425
12.4 Mutations are statistically random events......Page 426
Mutations arise without reference to the adaptive needs of the organism......Page 427
The surprisingly large number of new mutations in human gametes increases with father’s age......Page 428
12.5 Spontaneous and induced mutations have similar chemistries......Page 429
Some weak acids are mutagenic......Page 430
Highly reactive chemicals damage DNA......Page 431
Ultraviolet radiation absorbed by DNA is mutagenic......Page 432
Ionizing radiation is a potent mutagen......Page 433
Mismatch repair fixes incorrectly matched base pairs......Page 436
AP endonuclease repairs nucleotide sites at which a base has been lost......Page 438
Nucleotide excision repair works on a wide variety of DNA damage......Page 439
DNA damage bypass skips over damaged bases......Page 440
Double-stranded gaps can be repaired using a homologous molecule as a template......Page 441
12.7 Genetic tests are useful for detecting agents that cause mutations and cancer......Page 442
Chapter 13 Molecular Genetics of the Cell Cycle and Cancer......Page 448
13.1 The cell cycle is under genetic control......Page 449
Mutations affecting the cell cycle have helped to identify the key regulatory pathways......Page 450
The retinoblastoma protein controls the initiation of DNA synthesis......Page 451
Protein degradation also helps regulate the cell cycle......Page 452
13.2 Checkpoints in the cell cycle allow damaged cells to repair themselves or to self-destruct......Page 453
The p53 transcription factor is a key player in the DNA damage checkpoint......Page 454
The centrosome duplication checkpoint and the spindle checkpoint function to maintain the normal complement of chromosomes......Page 457
13.3 Cancer cells have a small number of mutations that prevent normal checkpoint function......Page 458
Proto-oncogenes normally function to promote cell proliferation or to prevent apoptosis......Page 460
Tumor-suppressor genes normally act to inhibit cell proliferation or to promote apoptosis......Page 462
Cancer initiation and progression occur through mutations that allow affected cells to evade normal cell-cycle checkpoints......Page 463
Retinoblastoma is an inherited cancer syndrome associated with loss of heterozygosity in the tumor cells......Page 466
13.5 Acute leukemias are proliferative diseases of white blood cells and their precursors......Page 467
the human connection Two Hits, Two Errors......Page 468
Some acute leukemias result from a chromosomal translocation that fuses a transcription factor with a leukocyte regulatory sequence......Page 469
Other acute leukemias result from a chromosomal translocation that fuses two genes to create a novel chimeric gene......Page 470
Chapter 14 Molecular Evolution and Population Genetics......Page 475
The ancestral history of species is recorded in their genome sequences......Page 476
A gene tree is a diagram of the inferred ancestral history of a group of gene sequences......Page 477
Rates of evolution can differ dramatically from one protein to another......Page 478
Rates of evolution of nucleotide sites differ according to their function......Page 479
New genes usually evolve through duplication and divergence......Page 480
14.2 Genotypes may differ in frequency from one population to another......Page 481
Allele frequencies are estimated from genotype frequencies......Page 482
The allele frequencies among gametes equal those among reproducing adults......Page 483
14.3 Random mating means that mates pair without regard to genotype......Page 484
The Hardy–Weinberg principle has important implications for population genetics......Page 485
If an allele is rare, it is found mostly in heterozygous genotypes......Page 486
Hardy–Weinberg frequencies can be extended to multiple alleles......Page 487
X-linked genes are a special case because males have only one X chromosome......Page 488
14.4 Highly polymorphic sequences are used in DNA typing......Page 489
DNA exclusions are definitive......Page 491
14.5 Inbreeding means mating between relatives......Page 492
Inbreeding results in an excess of homozygotes compared with random mating......Page 493
14.7 Mutation and migration bring new alleles into populations......Page 494
Fitness is the relative ability of genotypes to survive and reproduce......Page 495
Allele frequencies change slowly when alleles are either very rare or very common......Page 496
the human connection Resistance in the Blood......Page 497
Occasionally the heterozygote is the superior genotype......Page 498
14.9 Some changes in allele frequency are random......Page 499
Endangered species lose genetic variation......Page 500
14.10 Mitochondrial DNA is maternally inherited......Page 501
Modern human populations originated in subsaharan Africa approximately 200,000 years ago......Page 502
Chapter 15 The Genetic Basis of Complex Traits......Page 509
15.1 Complex traits are determined by multiple genes and the environment......Page 510
The distribution of a trait in a population implies nothing about its inheritance......Page 511
The genotypic variance results from differences in genotype......Page 514
The environmental variance results from differences in environment......Page 516
Genotype and environment can interact, or they can be associated......Page 518
The broad-sense heritability includes all genetic effects combined......Page 519
15.3 Artificial selection is a form of “managed evolution.”......Page 520
The narrow-sense heritability is usually the most important in artificial selection......Page 521
There are limits to the improvement that can be achieved by artificial selection......Page 523
Covariance is the tendency for traits to vary together......Page 524
The most common disorders in human families are multifactorial......Page 525
15.5 Pedigree studies of genetic polymorphisms are used to map loci for quantitative traits......Page 526
Complex traits are usually influenced by many genes, most with small effects......Page 527
the human connection Pinch of This and a Smidgen of That......Page 530
Readiness Review......Page 537
Answers for Even-Numbered Problems......Page 623
Word Roots, Prefixes, Suffixes, and Combining Forms......Page 633
Glossary......Page 637
Index......Page 657