| Preface |
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xii | |
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1 The Genetics Revolution |
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1 | (24) |
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1.1 The Birth of Genetics |
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2 | (7) |
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Gregor Mendel--A monk in the garden |
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3 | (1) |
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4 | (4) |
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The central dogma of molecular biology |
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8 | (1) |
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1.2 After Cracking the Code |
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9 | (3) |
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9 | (1) |
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Tools for genetic analysis |
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10 | (2) |
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12 | (13) |
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From classical genetics to medical genomics |
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12 | (2) |
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Investigating mutation and disease risk |
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14 | (2) |
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When rice gets its feet a little too wet |
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16 | (2) |
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Recent evolution in humans |
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18 | (2) |
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The complex genetics of color blindness |
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20 | (5) |
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PART I CORE PRINCIPLES IN TRANSMISSION GENTICS |
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25 | (207) |
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2 Single-Gene Inheritance |
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29 | (50) |
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2.1 Single-Gene Inheritance Patterns |
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32 | (4) |
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Mendel's pioneering experiments |
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32 | (1) |
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Mendel's law of equal segregation |
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33 | (3) |
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2.2 Genes and Chromosomes |
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36 | (5) |
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Single-gene inheritance in diploids |
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38 | (2) |
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Single-gene inheritance in haploids |
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40 | (1) |
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2.3 The Molecular Basis of Mendelian Inheritance Patterns |
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41 | (4) |
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Structural differences between alleles at the molecular level |
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41 | (1) |
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Molecular aspects of gene transmission |
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41 | (1) |
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Alleles at the molecular level |
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42 | (3) |
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2.4 Some Genes Discovered by Observing Segregation Ratios |
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45 | (3) |
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A gene active in the development of flower color |
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46 | (1) |
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A gene for wing development |
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46 | (1) |
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A gene for hyphal branching |
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47 | (1) |
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Predicting progeny proportions or parental genotypes by applying the principles of single-gene inheritance |
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47 | (1) |
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2.5 Sex-Linked Single-Gene Inheritance Patterns |
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48 | (4) |
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48 | (1) |
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Sex-linked patterns of inheritance |
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49 | (1) |
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49 | (3) |
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2.6 Human Pedigree Analysis |
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52 | (27) |
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Autosomal recessive disorders |
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53 | (2) |
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Autosomal dominant disorders |
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55 | (1) |
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56 | (2) |
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X-linked recessive disorders |
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58 | (2) |
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X-linked dominant disorders |
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60 | (1) |
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60 | (1) |
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Calculating risks in pedigree analysis |
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60 | (19) |
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3 Independent Assortment Of Genes |
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79 | (34) |
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3.1 Mendel's Law of Independent Assortment |
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81 | (3) |
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3.2 Working with Independent Assortment |
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84 | (6) |
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Predicting progeny ratios |
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85 | (1) |
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Using the chi-square test on monohybrid and dihybrid ratios |
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86 | (2) |
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88 | (1) |
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89 | (1) |
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3.3 The Chromosomal Basis of Independent Assortment |
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90 | (5) |
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Independent assortment in diploid organisms |
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91 | (1) |
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Independent assortment in haploid organisms |
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91 | (2) |
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93 | (2) |
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3.4 Polygenic Inheritance |
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95 | (2) |
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3.5 Organelle Genes: Inheritance Independent of the Nucleus |
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97 | (16) |
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Patterns of inheritance in organelles |
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98 | (1) |
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99 | (2) |
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Cytoplasmic mutations in humans |
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101 | (1) |
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mtDNA in evolutionary studies |
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102 | (11) |
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4 Mapping Eukaryote Chromosomes By Recombination |
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113 | (40) |
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4.1 Diagnostics of Linkage |
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115 | (4) |
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Using recombinant frequency to recognize linkage |
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115 | (2) |
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How crossovers produce recombinants for linked genes |
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117 | (1) |
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Linkage symbolism and terminology |
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117 | (1) |
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Evidence that crossing over is a breakage-and-rejoining process |
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117 | (1) |
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Evidence that crossing over takes place at the four-chromatid stage |
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118 | (1) |
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Multiple crossovers can include two or more than two chromatids |
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118 | (1) |
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4.2 Mapping by Recombinant Frequency |
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119 | (11) |
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119 | (3) |
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122 | (1) |
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Deducing gene order by inspection |
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123 | (1) |
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124 | (5) |
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Using ratios as diagnostics |
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129 | (1) |
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4.3 Mapping with Molecular Markers |
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130 | (1) |
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4.4 Using the Chi-Square Test to Infer Linkage |
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131 | (1) |
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4.5 The Molecular Mechanism of Crossing Over |
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132 | (2) |
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4.6 Using Recombination-Based Maps in Conjunction with Physical Maps |
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134 | (19) |
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153 | (40) |
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5.1 Interactions Between the Alleles of a Single Gene: Variations on Dominance |
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154 | (8) |
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Complete dominance and recessiveness |
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154 | (2) |
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156 | (1) |
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156 | (2) |
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158 | (2) |
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Penetrance and expressivity |
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160 | (2) |
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5.2 Interaction of Genes in Pathways |
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162 | (2) |
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Biosynthetic pathways in Neurospora |
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162 | (1) |
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Gene interaction in other types of pathways |
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163 | (1) |
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5.3 Inferring Gene Interactions |
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164 | (29) |
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Sorting mutants using the complementation test |
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165 | (1) |
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Analyzing double mutants of random mutations |
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166 | (27) |
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6 The Genetics Of Bacteria And Their Viruses |
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193 | (39) |
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6.1 Working with Microorganisms |
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195 | (2) |
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6.2 Bacterial Conjugation |
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197 | (11) |
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197 | (2) |
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Discovery of the fertility factor (F) |
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199 | (1) |
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200 | (3) |
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Mapping of bacterial chromosomes |
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203 | (3) |
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F plasmids that carry genomic fragments |
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206 | (1) |
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206 | (2) |
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6.3 Bacterial Transformation |
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208 | (1) |
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The nature of transformation |
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208 | (1) |
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Chromosome mapping using transformation |
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209 | (1) |
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6.4 Bacteriophage Genetics |
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209 | (4) |
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Infection of bacteria by phages |
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209 | (2) |
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Mapping phage chromosomes by using phage crosses |
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211 | (2) |
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213 | (4) |
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Discovery of transduction |
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213 | (1) |
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213 | (2) |
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215 | (1) |
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Mechanism of specialized transduction |
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216 | (1) |
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6.6 Physical Maps and Linkage Maps Compared |
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217 | (15) |
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PART II CORE PRINCIPLES IN MOLECULAR AND DEVEOPMENTAL GENETICS |
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232 | (266) |
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7 DNA: Structure And Replication |
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239 | (28) |
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7.1 DNA Is the Genetic Material |
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241 | (2) |
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The discovery of bacterial transformation: the Griffith experiment |
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241 | (1) |
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Evidence that DNA is the genetic material in bacteria: the Avery, MacLeod, and McCarty experiments |
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242 | (1) |
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Evidence that DNA is the genetic material in phage: the Hershey-Chase experiment |
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242 | (1) |
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243 | (6) |
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DNA structure before Watson and Crick |
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244 | (2) |
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The DNA double helix structure: Watson and Crick |
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246 | (3) |
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7.3 DNA Replication Is Semiconservative |
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249 | (2) |
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Evidence that DNA replication is semiconservative: the Meselson-Stahl experiment |
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250 | (1) |
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Evidence for a replication fork: the Cairns experiment |
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250 | (1) |
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7.4 DNA Replication in Bacteria |
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251 | (7) |
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Unwinding the DNA double helix |
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251 | (1) |
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Assembling the replisome: replication initiation |
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252 | (1) |
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DNA polymerases catalyze DNA chain elongation |
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253 | (1) |
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DNA replication is semidiscontinuous |
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254 | (1) |
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DNA replication is accurate and rapid |
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255 | (3) |
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7.5 DNA Replication in Eukaryotes |
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258 | (9) |
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Eukaryotic origins of replication |
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258 | (1) |
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DNA replication and the yeast cell cycle |
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258 | (1) |
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Replication origins in higher eukaryotes |
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259 | (1) |
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Telomeres and telomerase: replication termination |
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260 | (7) |
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8 RNA: Transcription, Processing, And Decay |
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267 | (34) |
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269 | (2) |
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RNA is the information-carrying intermediate between DNA and proteins |
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269 | (1) |
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Consequences of the distinct chemical properties of RNA |
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270 | (1) |
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270 | (1) |
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8.2 Transcription and Decay of mRNA in Bacteria |
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271 | (6) |
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Overview: DNA as transcription template |
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272 | (1) |
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273 | (3) |
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276 | (1) |
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8.3 Transcription in Eukaryotes |
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277 | (6) |
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Transcription initiation in eukaryotes |
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277 | (4) |
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RNA polymerase II transcription elongation |
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281 | (1) |
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Transcription termination in eukaryotes |
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281 | (2) |
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8.4 Processing of mRNA in Eukaryotes |
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283 | (8) |
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283 | (1) |
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284 | (1) |
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The discovery of splicing |
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284 | (1) |
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284 | (3) |
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snRNAs in the spliceosome may carry out the catalytic steps of splicing |
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287 | (1) |
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Alternative splicing can expand the proteome |
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288 | (2) |
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290 | (1) |
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RNA nucleotide modification |
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290 | (1) |
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RNA export from the nucleus |
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291 | (1) |
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8.5 Decay of mRNA in Eukaryotes |
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291 | (10) |
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292 | (1) |
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The discovery of RNA interference (RNAi) |
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292 | (2) |
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siRNA-mediated RNA decay and transcriptional silencing |
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294 | (1) |
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RNAi protects the genome from foreign DNA |
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295 | (6) |
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9 Proteins And Their Synthesis |
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301 | (30) |
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303 | (3) |
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306 | (4) |
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A degenerate three-letter genetic code specifies the 20 amino acids |
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306 | (1) |
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The genetic code is nonoverlapping and continuous |
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306 | (1) |
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307 | (2) |
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309 | (1) |
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Degeneracy of the genetic code limits the effects of point mutations |
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309 | (1) |
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310 | (5) |
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310 | (2) |
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Wobble base pairing allows tRNAs to recognize more than one codon |
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312 | (1) |
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Ribosome structure and function |
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313 | (2) |
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315 | (5) |
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315 | (3) |
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318 | (1) |
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319 | (1) |
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Nonsense suppressor mutations |
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320 | (1) |
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9.5 Translational and Post-Translational Regulation |
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320 | (11) |
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321 | (1) |
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Post-translational modification of amino acid side chains |
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322 | (2) |
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324 | (7) |
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10 Gene Isolation And Manipulation |
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331 | (38) |
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10.1 Detecting and Quantifying DNA, RNA, and Protein |
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334 | (8) |
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Detecting and quantifying molecules by Southern, Northern, and Western blot analysis |
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334 | (5) |
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Detecting and amplifying DNA by the polymerase chain reaction |
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339 | (3) |
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10.2 Generating Recombinant DNA |
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342 | (9) |
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342 | (5) |
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347 | (1) |
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Identifying a clone of interest from a genomic or cDNA library |
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347 | (1) |
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Genomic and cDNA clones are used in different ways |
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348 | (1) |
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349 | (2) |
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351 | (2) |
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353 | (16) |
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Genetic engineering in Saccharomyces cerevisiae |
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354 | (1) |
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Genetic engineering in plants |
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355 | (1) |
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Genetic engineering in animals |
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356 | (4) |
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CRISPR-Cas9 genome engineering |
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360 | (9) |
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11 Regulation Of Gene Expression In Bacteria And Their Viruses |
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369 | (30) |
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371 | (4) |
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The basics of bacterial transcriptional regulation: genetic switches |
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371 | (1) |
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A first look at the lac regulatory circuit |
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372 | (3) |
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11.2 Discovery of the lac System: Negative Regulation |
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375 | (4) |
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Genes controlled together |
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375 | (1) |
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Genetic evidence for the operator and repressor |
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375 | (2) |
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Genetic evidence for allostery |
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377 | (1) |
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Genetic analysis of the lac promoter |
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378 | (1) |
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Molecular characterization of the Lac repressor and the lac operator |
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378 | (1) |
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11.3 Catabolite Repression of the lac Operon: Positive Regulation |
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379 | (4) |
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The basics of lac catabolite repression: choosing the best sugar to metabolize |
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379 | (2) |
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The structures of target DNA sites |
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381 | (1) |
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A summary of the lac operon |
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382 | (1) |
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11.4 Dual Positive and Negative Regulation: The Arabinose Operon |
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383 | (1) |
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11.5 Metabolic Pathways and Additional Levels of Regulation: Attenuation |
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384 | (2) |
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11.6 Bacteriophage Life Cycles: More Regulators, Complex Operons |
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386 | (6) |
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Regulation of the bacteriophage X life cycle |
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386 | (3) |
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Molecular anatomy of the genetic switch |
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389 | (2) |
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Sequence-specific binding of regulatory proteins to DNA |
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391 | (1) |
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11.7 Alternative Sigma Factors Regulate Large Sets of Genes |
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392 | (7) |
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12 Regulation Of Transcription In Eukaryotes |
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399 | (28) |
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12.1 Transcription Factors Regulate Transcription |
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400 | (6) |
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Transcription factors bind distal and proximal enhancers |
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401 | (1) |
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Transcription factors: lessons from the yeast GAL system |
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402 | (1) |
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Gal4 domains function independently of one another |
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403 | (1) |
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404 | (1) |
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Combinatorial control of transcription: lessons from yeast mating type |
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405 | (1) |
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406 | (4) |
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407 | (1) |
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407 | (1) |
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407 | (3) |
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12.3 Chromatin Regulates Transcription |
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410 | (8) |
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Histone modification: a type of chromatin modification |
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410 | (1) |
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The histone code hypothesis |
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411 | (1) |
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DNA modification: another type of chromatin modification |
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412 | (2) |
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414 | (1) |
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Connecting chromatin structure to transcription: lessons from the Interferon-/) gene |
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415 | (3) |
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12.4 Chromatin in Epigenetic Regulation |
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418 | (9) |
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418 | (1) |
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Position-effect variegation |
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418 | (2) |
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420 | (1) |
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X-chromosome inactivation |
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421 | (6) |
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13 The Genetic Control Of Development |
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427 | (34) |
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13.1 The Genetic Approach to Development |
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429 | (3) |
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13.2 The Genetic Toolkit for Drosophila Development |
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432 | (6) |
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Classification of genes by developmental function |
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432 | (1) |
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Homeotic genes and segmental identity |
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432 | (1) |
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Organization and expression of Hox genes |
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433 | (2) |
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435 | (1) |
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Clusters of Hox genes control development in most animals |
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436 | (2) |
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13.3 Defining the Entire Toolkit |
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438 | (4) |
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439 | (1) |
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Expression of toolkit genes |
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439 | (3) |
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13.4 Spatial Regulation of Gene Expression in Development |
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442 | (6) |
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Maternal gradients and gene activation |
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442 | (1) |
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Drawing stripes: integration of gap-protein inputs |
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443 | (1) |
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Making segments different: integration of Hox inputs |
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444 | (4) |
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13.5 Post-transcriptional Regulation of Gene Expression in Development |
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448 | (5) |
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RNA splicing and sex determination in Drosophila |
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448 | (1) |
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Regulation of mRNA translation and cell lineage in C. elegans |
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449 | (1) |
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Translational control in the early embryo |
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449 | (3) |
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miRNA control of developmental timing in C. elegans and other species |
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452 | (1) |
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13.6 From Flies to Fingers, Feathers, and Floor Plates: The Many Roles of Individual Toolkit Genes |
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453 | (2) |
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13.7 Development and Disease |
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455 | (6) |
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455 | (1) |
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455 | (1) |
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Cancer as a developmental disease |
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456 | (5) |
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461 | (37) |
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14.1 The Genomics Revolution |
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463 | (2) |
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14.2 Obtaining the Sequence of a Genome |
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465 | (7) |
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Turning sequence reads into an assembled sequence |
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465 | (1) |
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466 | (1) |
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Traditional WGS sequencing |
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466 | (2) |
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Next-generation WGS sequencing |
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468 | (2) |
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Whole-genome-sequence assembly |
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470 | (2) |
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14.3 Bioinformatics: Meaning from Genomic Sequence |
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472 | (4) |
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The nature of the information content of DNA |
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473 | (1) |
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Deducing the protein-encoding genes from genomic sequence |
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473 | (3) |
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14.4 The Structure of the Human Genome |
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476 | (3) |
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Noncoding functional elements in the genome |
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477 | (2) |
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14.5 The Comparative Genomics of Humans with Other Species |
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479 | (5) |
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479 | (2) |
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481 | (1) |
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Comparative genomics of chimpanzees and humans |
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482 | (2) |
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14.6 Comparative Genomics and Human Medicine |
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484 | (4) |
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The evolutionary history of human disease genes |
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484 | (1) |
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The exome and personalized genomics |
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485 | (1) |
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Comparative genomics of nonpathogenic and pathogenic E coli |
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486 | (2) |
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14.7 Functional Genomics and Reverse Genetics |
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488 | (10) |
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489 | (2) |
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491 | (7) |
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PART III CORE PRINCIPLES IN MUTATION, VARIATION, AND EVOLUTION |
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498 | (215) |
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15 DNA Damage, Repair, And Mutation |
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501 | (26) |
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15.1 Molecular Consequences of Point Mutations |
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503 | (3) |
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The types of point mutations |
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503 | (1) |
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The molecular consequences of a point mutation in an open reading frame |
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503 | (2) |
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The molecular consequences of a point mutation in a noncoding region |
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505 | (1) |
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15.2 Molecular Basis of Spontaneous Mutations |
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506 | (5) |
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Evidence for spontaneous mutations: the Luria and Delbruck fluctuation test |
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506 | (1) |
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Mechanisms of spontaneous mutations |
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506 | (5) |
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15.3 Molecular Basis of Induced Mutations |
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511 | (4) |
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Mechanisms of induced mutagenesis |
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511 | (3) |
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Identifying mutagens in the environment: the Ames test |
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514 | (1) |
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15.4 DNA Repair Mechanisms |
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515 | (12) |
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Direct repair of damaged DNA |
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516 | (1) |
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516 | (1) |
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Nucleotide excision repair |
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517 | (2) |
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519 | (1) |
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520 | (1) |
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Repair of double-strand breaks |
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521 | (6) |
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16 The Dynamic Genome: Transposable Elements |
|
|
527 | (30) |
|
16.1 Discovery of Transposable Elements in Maize |
|
|
529 | (5) |
|
McClintock's experiments: the Ds element |
|
|
530 | (3) |
|
Ac (Activator) and Ds (Dissociation) today |
|
|
533 | (1) |
|
Transposable elements: only in maize? |
|
|
533 | (1) |
|
16.2 Transposable Elements in Bacteria |
|
|
534 | (4) |
|
Evidence for transposable elements in bacteria |
|
|
534 | (1) |
|
Simple and composite transposons |
|
|
535 | (1) |
|
Mechanism of transposition |
|
|
536 | (2) |
|
16.3 Transposable Elements in Eukaryotes |
|
|
538 | (7) |
|
|
|
538 | (3) |
|
|
|
541 | (1) |
|
Utility of DNA transposons as tools for genetic research |
|
|
542 | (3) |
|
16.4 The Dynamic Genome: More Transposable Elements Than Ever Imagined |
|
|
545 | (4) |
|
Large genomes are largely transposable elements |
|
|
545 | (1) |
|
Transposable elements in the human genome |
|
|
545 | (2) |
|
Plants: LTR-retrotransposons thrive in large genomes |
|
|
547 | (1) |
|
|
|
547 | (2) |
|
16.5 Regulation of Transposable Element Movement by the Host |
|
|
549 | (8) |
|
RNAi silencing of transposable elements |
|
|
549 | (1) |
|
|
|
550 | (7) |
|
17 Large-Scale Chromosomal Changes |
|
|
557 | (46) |
|
17.1 Changes in Chromosome Number |
|
|
559 | (15) |
|
|
|
559 | (5) |
|
|
|
564 | (6) |
|
The concept of gene balance |
|
|
570 | (4) |
|
17.2 Changes in Chromosome Structure |
|
|
574 | (12) |
|
|
|
576 | (2) |
|
|
|
578 | (1) |
|
|
|
579 | (3) |
|
Reciprocal translocations |
|
|
582 | (2) |
|
Robertsonian translocations |
|
|
584 | (1) |
|
Applications of inversions and translocations |
|
|
584 | (2) |
|
17.3 Phenotypic Consequences of Chromosomal Changes |
|
|
586 | (17) |
|
Chromosome rearrangements and evolution |
|
|
586 | (1) |
|
Chromosome rearrangements and cancer |
|
|
587 | (1) |
|
Overall incidence of human chromosome mutations |
|
|
588 | (15) |
|
|
|
603 | (40) |
|
18.1 Detecting Genetic Variation |
|
|
604 | (5) |
|
Single nucleotide polymorphisms (SNPs) |
|
|
605 | (1) |
|
|
|
606 | (1) |
|
|
|
606 | (2) |
|
Other sources and forms of variation |
|
|
608 | (1) |
|
18.2 The Gene-Pool Concept and the Hardy-Weinberg Law |
|
|
609 | (4) |
|
|
|
613 | (5) |
|
|
|
613 | (1) |
|
|
|
614 | (1) |
|
|
|
614 | (1) |
|
The inbreeding coefficient |
|
|
615 | (2) |
|
Population size and inbreeding |
|
|
617 | (1) |
|
18.4 Genetic Variation and Its Measurement |
|
|
618 | (3) |
|
18.5 The Modulation of Genetic Variation |
|
|
621 | (13) |
|
New alleles enter the population: mutation and migration |
|
|
621 | (1) |
|
Recombination and linkage disequilibrium |
|
|
622 | (1) |
|
Genetic drift and population size |
|
|
623 | (5) |
|
|
|
628 | (2) |
|
|
|
630 | (3) |
|
Balance between mutation and drift |
|
|
633 | (1) |
|
Balance between mutation and selection |
|
|
633 | (1) |
|
18.6 Biological and Social Applications |
|
|
634 | (9) |
|
|
|
634 | (1) |
|
Calculating disease risks |
|
|
635 | (1) |
|
|
|
635 | (8) |
|
19 The Inheritance Of Complex Traits |
|
|
643 | (38) |
|
19.1 Measuring Quantitative Variation |
|
|
645 | (3) |
|
Types of traits and inheritance |
|
|
645 | (1) |
|
|
|
645 | (1) |
|
|
|
646 | (1) |
|
|
|
647 | (1) |
|
19.2 A Simple Genetic Model for Quantitative Traits |
|
|
648 | (4) |
|
Genetic and environmental deviations |
|
|
649 | (1) |
|
Genetic and environmental variances |
|
|
649 | (2) |
|
Correlation between variables |
|
|
651 | (1) |
|
19.3 Broad-Sense Heritability: Nature versus Nurture |
|
|
652 | (3) |
|
Measuring heritability in humans using twin studies |
|
|
653 | (2) |
|
19.4 Narrow-Sense Heritability: Predicting Phenotypes |
|
|
655 | (8) |
|
Gene action and the transmission of genetic variation |
|
|
656 | (1) |
|
The additive and dominance effects |
|
|
656 | (1) |
|
A model with additivity and dominance |
|
|
657 | (3) |
|
Narrow-sense heritability |
|
|
660 | (1) |
|
Predicting offspring phenotypes |
|
|
661 | (1) |
|
Selection on complex traits |
|
|
662 | (1) |
|
19.5 Mapping QTL in Populations with Known Pedigrees |
|
|
663 | (6) |
|
The basic method for QTL mapping |
|
|
664 | (3) |
|
|
|
667 | (2) |
|
19.6 Association Mapping in Random-Mating Populations |
|
|
669 | (12) |
|
The basic method for GWAS |
|
|
669 | (2) |
|
GWA, genes, disease, and heritability |
|
|
671 | (10) |
|
20 Evolution Of Genes, Traits, And Species |
|
|
681 | (32) |
|
20.1 Evolution by Natural Selection |
|
|
684 | (2) |
|
20.2 Natural Selection in Action: An Exemplary Case |
|
|
686 | (3) |
|
The selective advantage of Hbs |
|
|
686 | (1) |
|
The molecular origins of Hbs |
|
|
687 | (2) |
|
|
|
689 | (3) |
|
The development of the neutral theory of evolution |
|
|
689 | (1) |
|
The rate of neutral substitutions |
|
|
690 | (1) |
|
The signature of purifying selection on DNA sequences |
|
|
690 | (1) |
|
The signature of positive selection on DNA sequences |
|
|
691 | (1) |
|
20.4 Evolution of Genes and Genomes |
|
|
692 | (5) |
|
|
|
692 | (1) |
|
The fate of duplicated genes |
|
|
692 | (2) |
|
The fate of duplicated genomes |
|
|
694 | (3) |
|
|
|
697 | (6) |
|
Adaptive changes in a pigment-regulating protein |
|
|
697 | (1) |
|
|
|
698 | (1) |
|
Regulatory-sequence evolution |
|
|
699 | (1) |
|
Loss of characters through regulatory-sequence evolution |
|
|
700 | (2) |
|
Regulatory evolution in humans |
|
|
702 | (1) |
|
20.6 Evolution of Species |
|
|
703 | (10) |
|
|
|
703 | (1) |
|
Mechanisms of reproductive isolation |
|
|
703 | (1) |
|
Genetics of reproductive isolation |
|
|
704 | (9) |
| A Brief Guide To Model Organisms |
|
713 | (20) |
| Appendix A Genetic Nomenclature |
|
733 | (1) |
| Appendix B Bioinformatic Resources for Genetics and Genomics |
|
734 | (2) |
| Glossary |
|
736 | (21) |
| Answers To Selected Problems |
|
757 | (13) |
| Index |
|
770 | |
