Essential genetics and genomics

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Essential Genetics and Genomics
Copyright
Brief Contents
Contents
Preface
The Student Experience
Readiness Assessment and Readiness Review
Acknowledgments
About the Author
For the Student
Chapter 1 The Genetic Code of Genes and Genomes
	1.1 DNA is the molecule of heredity
		Genetic traits can be altered by treatment with pure DNA
		Transmission of DNA is the link between generations
	1.2 The structure of DNA is a double helix composed of two intertwined strands
		A central feature of double-stranded DNA is complementary base pairing
		In replication, each parental DNA strand directs the synthesis of a new partner strand
	1.3 Genes affect organisms through the action of proteins
		Enzyme defects result in inborn errors of metabolism
		A defective enzyme results from a mutant gene
		Genetic analysis led to the one gene–one enzyme hypothesis
	the human connection One Gene, One Enzyme
		Mutant screens sometimes isolate different mutations in the same gene
		A complementation test identifies mutations in the same gene
		Genetic analysis can be applied to the study of any complex biological process
	1.4 Genes specify proteins by means of a genetic code
		One of the DNA strands directs the synthesis of a molecule of RNA
		A molecule of RNA directs the synthesis of a polypeptide chain
		The genetic code is a triplet code
	1.5 Genes change by mutation
	1.6 Most traits are complex traits affected by multiple genetic and environmental factors
	1.7 Evolution means continuity of life with change
		Groups of related organisms descend from a common ancestor
		The molecular unity of life is seen in comparisons of genomes
Chapter 2 Transmission Genetics: Heritage from Mendel
	2.1 Mendel took a distinctly modern view of transmission genetics
		Mendel was careful in his choice of traits
		Reciprocal crosses yield the same types of offspring
		The wrinkled mutation causes an inborn error in starch synthesis
		Analysis of DNA puts Mendel’s experiments in a modern context
	2.2 Genes come in pairs, separate in gametes, and join randomly in fertilization
		Genes are physical entities that come in pairs
		The paired genes separate (segregate) in the formation of reproductive cells
		Gametes unite at random in fertilization
		Genotype means genetic endowment; phenotype means observed trait
		The progeny of the F2 generation support Mendel’s hypothesis
		The progeny of testcrosses also support Mendel’s hypothesis
	2.3 The alleles of different genes segregate independently
		The F2 genotypes in a dihybrid cross conform to Mendel’s prediction
		The progeny of testcrosses show the result of independent assortment
	2.4 Chance plays a central role in Mendelian genetics
		The addition rule applies to mutually exclusive possibilities
		The multiplication rule applies to independent possibilities
	2.5 The results of segregation can be observed in human pedigrees
		Most differences in human genes are not harmful
	2.6 Simple dominance is not always observed
		Flower color in snapdragons illustrates incomplete dominance
		The human ABO blood groups illustrate both dominance and codominance
		A mutant gene can affect more than one trait
		A mutant gene is not always expressed in exactly the same way
	2.7 Epistasis can affect the observed ratios of phenotypes
	the human connection Blood Feud
Chapter 3 The Chromosomal Basis of Heredity
	3.1 Each species has a characteristic set of chromosomes
	3.2 The daughter cells of mitosis have identical chromosomes
		In mitosis, the replicated chromosomes align on the spindle, and the sister chromatids pull apart
	3.3 Meiosis results in gametes that differ genetically
		The first meiotic division reduces the chromosome number by half
		The second meiotic division is equational
	3.4 Eukaryotic chromosomes are highly coiled complexes of DNA and protein
		The nucleosome is the basic structural unit of chromatin
		Chromatin fibers form discrete chromosome territories in the nucleus
		The metaphase chromosome is a hierarchy of coiled coils
		Heterochromatin is rich in satellite DNA and low in gene content
	3.5 The centromere and telomere are essential parts of chromosomes
		The centromere is essential for chromosome segregation
		The telomere is essential for the stability of the chromosome tips
		Telomere length limits the number of cell doublings
	3.6 Genes are located in chromosomes
		Special chromosomes determine sex in many organisms
		X-linked genes are inherited according to sex
		Hemophilia is a classic example of human X-linked inheritance
	the human connection Sick of Telomeres
		In birds, moths, and butterflies, the sex chromosomes are reversed
		Experimental proof of the chromosome theory came from nondisjunction
	3.7 Genetic data analysis makes use of probability and statistics
		Progeny of crosses are predicted by the binomial probability formula
		Chi-square tests goodness of fit of observed to expected numbers
Chapter 4 Gene Linkage and Genetic Mapping
	4.1 Linked alleles tend to stay together in meiosis
		The degree of linkage is measured by the frequency of recombination
		The frequency of recombination is the same for coupling and repulsion heterozygotes
		The frequency of recombination differs from one gene pair to the next
		Recombination does not occur in Drosophila males
	4.2 Recombination results from crossing-over between linked alleles
		A linkage group is a genetic map of the genes in a chromosome
		Physical distance is often—but not always—correlated with map distance
		One crossover can undo the effects of another
	4.3 Double crossovers are revealed in three-point crosses
		Interference decreases the chance of multiple crossing-over
	4.4 Polymorphic DNA sequences are used in human genetic mapping
		Single-nucleotide polymorphisms (SNPs) are abundant in the human genome
		Gene dosage can differ owing to copy-number variation (CNV)
		Copy-number variation has helped human populations adapt to a high-starch diet
		Short tandem repeats (STRs) often differ in copy number
	the human connection Starch Contrast
	4.5 Tetrads contain all four products of meiosis
		Unordered tetrads have no relation to the geometry of meiosis
		Tetratype tetrads demonstrate that crossingover takes place at the four-strand stage of meiosis and is reciprocal
		Tetrad analysis affords a convenient test for linkage
		The geometry of meiosis is revealed in ordered tetrads
		Gene conversion suggests a molecular mechanism of recombination
	4.6 Recombination is initiated by a double-stranded break in DNA
		Recombination tends to take place at preferred positions in the genome
Chapter 5 Human Chromosomes and Chromosome Behavior
	5.1 Humans have 46 chromosomes in 23 pairs
		The standard human karyotype consists of 22 pairs of autosomes and two sex chromosomes
		Chromosomes with no centromere, or with two centromeres, are genetically unstable
		Dosage compensation adjusts the activity of X-linked genes in females
		The calico cat shows visible evidence of X-chromosome inactivation
		Some genes in the X chromosome are also present in the Y chromosome
		The pseudoautosomal region of the X and Y chromosomes has gotten progressively shorter in evolutionary time
		The history of human populations can be traced through studies of the Y chromosome
	5.2 Chromosome abnormalities are frequent in spontaneous abortions
		Down syndrome results from three copies of chromosome 21
		Trisomic chromosomes undergo abnormal segregation
		An extra X or Y chromosome usually has a relatively mild effect
		The rate of nondisjunction can be increased by chemicals in the environment
	the human connection Catch 21
	5.3 Chromosome rearrangements can have important genetic effects
		A chromosome with a deletion has genes missing
		Rearrangements are apparent in giant polytene chromosomes
		A chromosome with a duplication has extra genes
		Human color-blindness mutations result from unequal crossing-over
		Some reciprocal deletions and duplications are associated with reciprocal risks of autism and schizophrenia
		A chromosome with an inversion has some genes in reverse order
		Reciprocal translocations interchange parts between nonhomologous chromosomes
	5.4 Polyploid species have multiple sets of chromosomes
		Polyploids can arise from genome duplications occurring before or after fertilization
		Polyploids can include genomes from different species
	5.5 The grass family illustrates the importance of polyploidy and chromosome rearrangements in genome evolution
Chapter 6 DNA Structure, Replication, and Manipulation
	6.1 Genome size can differ tremendously, even among closely related organisms
	6.2 DNA is a linear polymer of four deoxyribonucleotides
	6.3 Duplex DNA is a double helix in which the bases form hydrogen bonds
	6.4 Replication uses each DNA strand as a template for a new one
		Nucleotides are added one at a time to the growing end of a DNA strand
		DNA replication is semiconservative: The parental strands remain intact
		DNA strands must unwind to be replicated
		Eukaryotic DNA molecules contain multiple origins of replication
	6.5 Many proteins participate in DNA replication
		Each new DNA strand or fragment is initiated by a short RNA primer
		DNA polymerase has a proofreading function that corrects errors in replication
		One strand of replicating DNA is synthesized in pieces
	the human connection Sickle-Cell Anemia: The First “Molecular Disease”
		Precursor fragments are joined together when they meet
		Synthesis of the leading strand and the lagging strand are coordinated
	6.6 Knowledge of DNA structure makes possible the manipulation of DNA molecules
		Single strands of DNA or RNA with complementary sequences can hybridize
		Restriction enzymes cleave duplex DNA at particular nucleotide sequences
	6.7 The polymerase chain reaction makes possible the amplification of a particular DNA fragment
	6.8 Chemical terminators and other methods are used to determine the base sequence
		The incorporation of a dideoxynucleotide terminates strand elongation
Chapter 7 The Genetics of Bacteria and Their Viruses
	7.1 Many DNA sequences in bacteria are mobile and can be transferred between individuals and among species
		A plasmid is an accessory DNA molecule, often a circle
		The F plasmid is a conjugative plasmid
		Insertion sequences and transposons play a key role in bacterial populations
		Nonconjugative plasmids can be mobilized by cointegration into conjugative plasmids
		Integrons have special site-specific recombinases for acquiring antibiotic-resistance cassettes
		Bacterial genomes can contain discrete regions of DNA from different sources
		Bacteria with resistance to multiple antibiotics are an increasing problem in public health
	7.2 Mutations that affect a cell’s ability to form colonies are often used in bacterial genetics
	7.3 Transformation results from the uptake of DNA and recombination
	7.4 In bacterial mating, DNA transfer is unidirectional
		The F plasmid can integrate into the bacterial chromosome
		Chromosome transfer begins at F and proceeds in one direction
		The unit of distance in the E. coli genetic map is the length of chromosomal DNA transferred in 1 minute
		Some F plasmids carry bacterial genes
	7.5 Some phages can transfer small pieces of bacterial DNA
	the human connection The Sex Life of Bacteria
	7.6 Bacteriophage DNA molecules in the same cell can recombine
		Bacteriophages form plaques on a lawn of bacteria
		Infection with two mutant bacteriophages yields recombinant progeny
	7.7 Lysogenic bacteriophages do not necessarily kill the host
		Specialized transducing phages carry a restricted set of bacterial genes
Chapter 8 The Molecular Genetics of Gene Expression
	8.1 Polypeptide chains are linear polymers of amino acids
		The proteins of humans and other vertebrates have a more complex domain structure than do the proteins of invertebrates
	8.2 The linear order of amino acids is encoded in a DNA base sequence
	8.3 The base sequence in DNA specifies the base sequence in an RNA transcript
		The chemical synthesis of RNA is similar to that of DNA
		Eukaryotes have several types of RNA polymerase
		Promoter recognition typically requires multiple DNA-binding proteins
		RNA polymerase is a molecular machine for transcription
		Messenger RNA directs the synthesis of a polypeptide chain
	8.4 RNA processing converts the original RNA transcript into messenger RNA
		Splicing removes introns from the RNA transcript
		Human genes tend to be very long even though they encode proteins of modest size
		Many exons code for distinct protein-folding domains
	8.5 Translation into a polypeptide chain takes place on a ribosome
		In eukaryotes, initiation takes place by scanning the mRNA for an initiation codon
		Elongation takes place codon by codon
		A termination codon signals release of the finished polypeptide chain
		Proofreading and premature termination help ensure translational accuracy
		Most polypeptide chains fold correctly as they exit the ribosome
		Prokaryotes often encode multiple polypeptide chains in a single mRNA
	8.6 The genetic code for amino acids is a triplet code
		Genetic evidence for a triplet code came from three-base insertions and deletions
		Most of the codons were determined from in vitro polypeptide synthesis
	the human connection Poly-U
		Redundancy and near-universality are principal features of the genetic code
		An aminoacyl-tRNA synthetase attaches an amino acid to its tRNA
		Much of the code’s redundancy comes from wobble in codon–anticodon pairing
	8.7 Several ribosomes can move in tandem along a messenger RNA
Chapter 9 Molecular Mechanisms of Gene Regulation
	9.1 Regulation of transcription is a common mechanism in prokaryotes
		In negative regulation, the default state of transcription is “on.”
		In positive regulation, the default state of transcription is “off.”
		Transcription sometimes occurs accidentally
	9.2 In prokaryotes, groups of adjacent genes are often transcribed as a single unit
		The first regulatory mutations that were discovered affected lactose metabolism
		Lactose-utilizing enzymes can be inducible (regulated) or constitutive
		Repressor shuts off messenger RNA synthesis
		The lactose operator is an essential site for repression
		The lactose promoter is an essential site for transcription
		The lactose operon contains linked structural genes and regulatory sequences
		Stochastic noise aids induction of the lactose operon
		The lactose operon is also subject to positive regulation
		Tryptophan biosynthesis is regulated by the tryptophan operon
	9.3 Gene activity can be regulated through transcriptional termination
		Attenuation allows for fine-tuning of transcriptional regulation
		Riboswitches combine with small molecules to control transcriptional termination
	9.4 Eukaryotes regulate transcription through transcriptional activator proteins, enhancers, and silencers
		Galactose metabolism in yeast illustrates transcriptional regulation
		Transcription is stimulated by transcriptional activator proteins
		Enhancers increase transcription; silencers decrease transcription
		Genome architecture consists of compact domains of associating DNA molecules
		The eukaryotic transcription complex includes numerous protein factors
		Chromatin-remodeling complexes prepare chromatin for transcription
		Some eukaryotic genes have alternative promoters
	9.5 Gene expression can be affected by heritable chemical modifications in the DNA
		Transcriptional inactivation is associated with heavy DNA methylation
		In mammals, some genes are imprinted by methylation in the germ line
	9.6 Regulation also takes place at the levels of RNA processing and decay
		The primary transcripts of many genes are alternatively spliced to yield different products
		The coding capacity of the human genome is enlarged by extensive alternative splicing
		Different messenger RNAs can differ in their persistence in the cell
		RNA interference results in the silencing of RNA transcripts
	the human connection Double Trouble
		Some long noncoding RNA transcripts function in gene regulation
	9.7 Regulation can also take place at the level of translation
		Small regulatory RNAs can control translation by base-pairing with the messenger RNA
Chapter 10 Genomics, Proteomics, and Genetic Engineering
	10.1 Genome sequencing has become rapid and inexpensive as a result of new technologies
		High-throughput DNA sequencing empowers personalized genomics
		A genome sequence without annotation is meaningless
		Comparison among genomes is an aid to annotation
		Ancient DNA indicates interbreeding between our ancestors and archaic human groups that became extinct
		Your genome sequence can help personalize your medical care
	the human connection Skeletons in Our Closet
	10.2 Genomics and proteomics reveal genome-wide patterns of gene expression and networks of protein interactions
		DNA microarrays and RNA-seq are used to estimate the relative level of gene expression of each gene in the genome
		Transcriptional profiling reveals groups of genes that are coordinately expressed during development
		Chromatin immunoprecipitation (ChIP) reveals protein–DNA interactions
		Yeast two-hybrid analysis reveals networks of protein interactions
	10.3 Recombinant DNA is produced by the manipulation of DNA fragments
		Restriction enzymes cleave DNA into fragments with defined ends
		Restriction fragments are joined end to end to produce recombinant DNA
		A vector is a carrier for recombinant DNA
		Vector and target DNA fragments are joined with DNA ligase
		A recombinant cDNA contains the coding sequence of a eukaryotic gene
		Loss of ß-galactosidase activity is often used to detect recombinant vectors
	10.4 CRISPR-Cas9 technology for gene editing has revolutionized genetic engineering
		CRISPR-Cas9 can be used to create knockout mutations of any gene
		CRISPR-Cas9 can be used to edit the sequence of any gene
		Methods for using CRISPR-Cas9 depend on the organism
		CRISPR-Cas9 can also be used in plants
	10.5 Genetic engineering is applied in medicine, industry, agriculture, and research
		Animal growth rate can be genetically engineered
		Crop plants with improved nutritional qualities can be created
		The production of useful proteins is a primary impetus for recombinant DNA
Chapter 11 The Genetic Control of Development
	11.1 The determination of cell fate in C. elegans development is largely autonomous
		Development in C. elegans exhibits a fixed pattern of cell divisions and cell lineages
		Cell fate is determined by autonomous development and/or intercellular signaling
		Developmental mutations often affect cell lineages
		Transmembrane receptors often mediate signaling between cells
		Cells can determine the fate of other cells through ligands that bind with their transmembrane receptors
	11.2 Epistatic interactions between mutant alleles can help define signaling pathways
	11.3 Development in Drosophila illustrates progressive regionalization and specification of cell fate
		Mutations in a maternal-effect gene result in defective oocytes
		Embryonic pattern formation is under genetic control
	the human connection Distinguished Lineages
		Coordinate genes establish the main body axes
		Gap genes regulate other genes in broad anterior–posterior regions
		Pair-rule genes are expressed in alternating segments or parasegments
		Segment-polarity genes govern differentiation within segments
		Interactions among genes in the regulatory hierarchy ensure an orderly progression of developmental events
		Homeotic genes function in the specification of segment identity
		Hox genes are important master control genes in animal development
		Pax6 is a master regulator of eye development
	11.4 Floral development in Arabidopsis illustrates combinatorial control of gene expression
		Flower development in Arabidopsis is controlled by MADS box transcription factors
		Flower development in Arabidopsis is controlled by the combination of genes expressed in each concentric whorl
Chapter 12 Molecular Mechanisms of Mutation and DNA Repair
	12.1 Mutations are classified in a variety of ways
		Mutagens increase the chance that a gene undergoes mutation
		Germ-line mutations are inherited; somatic mutations are not
		Conditional mutations are expressed only under certain conditions
		Mutations can affect the amount or activity of the gene product, or the time or tissue specificity of expression
	12.2 Mutations result from changes in DNA sequence
		A base substitution replaces one nucleotide pair with another
		Mutations in protein-coding regions can change an amino acid, truncate the protein, or shift the reading frame
		Sickle-cell anemia results from a missense mutation that confers resistance to malaria
		In the human genome, some trinucleotide repeats have high rates of mutation
	12.3 Transposable elements are agents of mutation
		Some transposable elements transpose via a DNA intermediate, others via an RNA intermediate
		Transposable elements can cause mutations by insertion or by recombination
		Almost 50 percent of the human genome consists of transposable elements, most of them no longer able to transpose
	12.4 Mutations are statistically random events
		Mutations arise without reference to the adaptive needs of the organism
		The surprisingly large number of new mutations in human gametes increases with father’s age
		Mutations are nonrandom with respect to position in a gene or genome
	12.5 Spontaneous and induced mutations have similar chemistries
		Purine bases are susceptible to spontaneous loss
		Some weak acids are mutagenic
		A base analog masquerades as the real thing
		Highly reactive chemicals damage DNA
		Some agents cause base-pair additions or deletions
		Ultraviolet radiation absorbed by DNA is mutagenic
		Ionizing radiation is a potent mutagen
	12.6 Many types of DNA damage can be repaired
		Mismatch repair fixes incorrectly matched base pairs
		Base excision removes damaged bases from DNA
		AP endonuclease repairs nucleotide sites at which a base has been lost
	the human connection Damage Beyond Repair
		Nucleotide excision repair works on a wide variety of DNA damage
		Special enzymes repair damage to DNA caused by ultraviolet light
		DNA damage bypass skips over damaged bases
		Double-stranded gaps can be repaired using a homologous molecule as a template
	12.7 Genetic tests are useful for detecting agents that cause mutations and cancer
Chapter 13 Molecular Genetics of the Cell Cycle and Cancer
	13.1 The cell cycle is under genetic control
		Many genes are transcribed during the cell cycle just before their product is needed
		Mutations affecting the cell cycle have helped to identify the key regulatory pathways
		Cyclins and cyclin-dependent protein kinases propel the cell through the cell cycle
		The retinoblastoma protein controls the initiation of DNA synthesis
		Protein degradation also helps regulate the cell cycle
	13.2 Checkpoints in the cell cycle allow damaged cells to repair themselves or to self-destruct
		The p53 transcription factor is a key player in the DNA damage checkpoint
		The centrosome duplication checkpoint and the spindle checkpoint function to maintain the normal complement of chromosomes
	13.3 Cancer cells have a small number of mutations that prevent normal checkpoint function
		Proto-oncogenes normally function to promote cell proliferation or to prevent apoptosis
		Tumor-suppressor genes normally act to inhibit cell proliferation or to promote apoptosis
	13.4 Mutations that predispose to cancer can be inherited through the germ line
		Cancer initiation and progression occur through mutations that allow affected cells to evade normal cell-cycle checkpoints
		Retinoblastoma is an inherited cancer syndrome associated with loss of heterozygosity in the tumor cells
		Some inherited cancer syndromes result from defects in processes of DNA repair
	13.5 Acute leukemias are proliferative diseases of white blood cells and their precursors
	the human connection Two Hits, Two Errors
		Some acute leukemias result from a chromosomal translocation that fuses a transcription factor with a leukocyte regulatory sequence
		Other acute leukemias result from a chromosomal translocation that fuses two genes to create a novel chimeric gene
Chapter 14 Molecular Evolution and Population Genetics
	14.1 DNA and protein sequences contain information about the evolutionary relationships among species
		The ancestral history of species is recorded in their genome sequences
		A gene tree is a diagram of the inferred ancestral history of a group of gene sequences
		Rates of evolution can differ dramatically from one protein to another
		Rates of evolution of nucleotide sites differ according to their function
		The Ka/Ks  ratio can reveal selection acting across a protein-coding sequence
		New genes usually evolve through duplication and divergence
	14.2 Genotypes may differ in frequency from one population to another
		Allele frequencies are estimated from genotype frequencies
		The allele frequencies among gametes equal those among reproducing adults
	14.3 Random mating means that mates pair without regard to genotype
		The Hardy–Weinberg principle has important implications for population genetics
		If an allele is rare, it is found mostly in heterozygous genotypes
		Hardy–Weinberg frequencies can be extended to multiple alleles
		X-linked genes are a special case because males have only one X chromosome
	14.4 Highly polymorphic sequences are used in DNA typing
		DNA exclusions are definitive
	14.5 Inbreeding means mating between relatives
		Inbreeding results in an excess of homozygotes compared with random mating
	14.6 Evolution is accompanied by genetic changes in species
	14.7 Mutation and migration bring new alleles into populations
	14.8 Natural selection favors genotypes that are better able to survive and reproduce
		Fitness is the relative ability of genotypes to survive and reproduce
		Allele frequencies change slowly when alleles are either very rare or very common
		Selection can be balanced by new mutations
	the human connection Resistance in the Blood
		Occasionally the heterozygote is the superior genotype
	14.9 Some changes in allele frequency are random
		Endangered species lose genetic variation
	14.10 Mitochondrial DNA is maternally inherited
		Human mtDNA evolves changes in sequence at an approximately constant rate
		Modern human populations originated in subsaharan Africa approximately 200,000 years ago
Chapter 15 The Genetic Basis of Complex Traits
	15.1 Complex traits are determined by multiple genes and the environment
		Continuous, categorical, and threshold traits are usually multifactorial
		The distribution of a trait in a population implies nothing about its inheritance
	15.2 Variation in a trait can be separated into genetic and environmental components
		The genotypic variance results from differences in genotype
		The environmental variance results from differences in environment
		Genotype and environment can interact, or they can be associated
		There is no genotypic variance in a genetically homogeneous population
		The broad-sense heritability includes all genetic effects combined
		Twin studies are often used to assess genetic effects on variation in a trait
	15.3 Artificial selection is a form of “managed evolution.”
		The narrow-sense heritability is usually the most important in artificial selection
		There are limits to the improvement that can be achieved by artificial selection
		Inbreeding is generally harmful, and hybrids may be the best
	15.4 Genetic variation is revealed by correlations between relatives
		Covariance is the tendency for traits to vary together
		The additive genetic variance is transmissible; the dominance variance is not
		The most common disorders in human families are multifactorial
	15.5 Pedigree studies of genetic polymorphisms are used to map loci for quantitative traits
		Complex traits are usually influenced by many genes, most with small effects
		QTLs can also be identified by examining candidate genes
	the human connection Pinch of This and a Smidgen of That
Readiness Review
Answers for Even-Numbered Problems
Word Roots, Prefixes, Suffixes, and Combining Forms
Glossary
Index