Essential Genetics and Genomics

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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