List of Contributors |
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Chapter 1 Next Generation SequencingGeneral Information about the Technology, Possibilities, and Limitations |
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1 | (18) |
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NGS Versus Traditional (Sanger Sequencing) |
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2 | (1) |
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3 | (1) |
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3 | (1) |
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Sequence Assembly: De Novo Sequencing vs Resequencing |
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4 | (1) |
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Paired-End and Mate-Pair Libraries and Long Fragment Read Technology |
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5 | (1) |
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6 | (6) |
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6 | (2) |
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Semiconductor-based platforms |
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8 | (1) |
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Sequencing by the Oligo Ligation Detection (SOLiD) Platform |
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9 | (1) |
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Pyrosequencing on Roche/454 platforms |
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10 | (1) |
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Complete genomics analysis (CGATM) platform |
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10 | (1) |
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Single-Molecule Sequencing |
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11 | (1) |
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Targeted Resequencing/Enrichment Strategies |
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12 | (2) |
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Whole Exome Sequencing and Whole Genome Sequencing |
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14 | (1) |
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Limitations of NGS in Clinical Medicine |
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15 | (1) |
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16 | (1) |
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17 | (2) |
Chapter 2 Basic Bioinformatic Analyses of NGS Data |
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19 | (20) |
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20 | (1) |
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Input Sequence Preprocessing |
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21 | (2) |
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23 | (3) |
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Processing and Interpreting Mapping |
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26 | (1) |
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Insertions and Deletions Realignment |
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26 | (1) |
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Base Quality Recalibration |
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27 | (1) |
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27 | (5) |
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Major Approaches to the Variant Calling |
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28 | (1) |
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28 | (2) |
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30 | (2) |
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Software and Hardware Issues |
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32 | (3) |
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Computational Architecture |
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32 | (2) |
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34 | (1) |
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35 | (4) |
Chapter 3 Analysis of Structural Chromosome Variants by Next Generation Sequencing Methods |
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39 | (24) |
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Silviene Fabiana de Oliveira |
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39 | (1) |
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Structural Variants in the Human Genome |
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40 | (1) |
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Structural Variation and Human Disease |
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40 | (1) |
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Analysis of Structural Variation by Legacy Technologies |
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41 | (1) |
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Structural Variation and Next Generation Sequencing |
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42 | (1) |
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Methods for Estimation of Copy Number Variation from NGS Data |
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42 | (2) |
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Structural Variation, NGS, Cancer, and the Clinic |
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44 | (2) |
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NGS-Based Structural Variation Detection Software |
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46 | (5) |
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51 | (6) |
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57 | (1) |
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57 | (6) |
Chapter 4 Next Generation Sequencing in Oncology |
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63 | (12) |
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64 | (1) |
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65 | (7) |
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66 | (1) |
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Molecular Disease Classification |
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66 | (1) |
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67 | (1) |
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Testing in "Last-Resort" Patients |
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67 | (1) |
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Circulating Cell-Free Tumor DNA and Circulating Tumor Cells |
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67 | (2) |
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69 | (1) |
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Biomarkers in Clinical Decision-Making |
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70 | (1) |
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Current Obstacles Preventing NGS from Wide Application in Clinical Settings |
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70 | (1) |
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Targeted versus Genome-Wide Approach |
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71 | (1) |
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72 | (1) |
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Pros and Cons of Traditional versus NGS Sequencing Approach |
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72 | (1) |
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Challenges in Clinical Oncogenomics |
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72 | (1) |
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72 | (3) |
Chapter 5 Next Generation Sequencing in Hematological Disorders |
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75 | (22) |
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75 | (1) |
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Childhood and Adult Acute Lymphoblastic Leukemias |
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76 | (2) |
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T-Cell Acute Lymphoblastic Leukemia |
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78 | (1) |
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BCRABL1-like Acute Lymphoblastic Leukemia |
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79 | (1) |
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Hypodiploid Acute Lymphoblastic Leukemia |
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79 | (1) |
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Relapsed Acute Lymphoblastic Leukemia |
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80 | (1) |
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80 | (2) |
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Genetic Concept of Acute Myeloid Leukemia Pathogenesis |
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82 | (2) |
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BRAF Mutation in Hairy Cell Leukemia |
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84 | (1) |
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CSF3R Mutation in Chronic Neutrophilic Leukemia |
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84 | (1) |
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NGS in Chronic Lymphocytic Lymphoma |
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84 | (1) |
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85 | (2) |
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Inherited Bone Marrow Failure Syndromes |
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87 | (1) |
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87 | (1) |
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88 | (1) |
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Thrombocytopenia Absent Radius Syndrome |
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89 | (1) |
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89 | (1) |
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Commercial NGS-Based Assays for Clinical Use in Hematology Practice |
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90 | (1) |
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Implementation of NGS-Based Techniques in Clinical Practice in Hematology |
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91 | (1) |
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92 | (1) |
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92 | (5) |
Chapter 6 Next Generation Sequencing in Neurology and Psychiatry |
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97 | (40) |
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98 | (16) |
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Genetic Testing in Neurology and Psychiatry |
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98 | (3) |
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101 | (4) |
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105 | (2) |
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Hereditary Spastic Paraplegias |
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107 | (1) |
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108 | (2) |
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110 | (2) |
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Neurodegenerative Diseases with Dementia |
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112 | (2) |
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Neuropsychiatric Disorders |
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114 | (14) |
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114 | (2) |
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116 | (4) |
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Intellectual Disability and AutismA Practical Approach |
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120 | (1) |
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Genetic Testing in Autism and IDA Proposal |
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120 | (2) |
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122 | (2) |
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Major Psychiatric Disorders |
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124 | (4) |
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128 | (9) |
Chapter 7 Next Generation Sequencing in Dysmorphology |
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137 | (16) |
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DysmorphologyPast and Present |
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137 | (1) |
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Diagnostic Process in Dysmorphology |
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138 | (1) |
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Genetic Testing in Dysmorphology |
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139 | (2) |
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NGS Testing in Dysmorphology and Rare Multiple Congenital Defects Syndromes |
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141 | (4) |
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145 | (1) |
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146 | (1) |
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NGS and Screening of Rare Disorders in Newborns |
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146 | (1) |
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147 | (1) |
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147 | (1) |
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148 | (5) |
Chapter 8 Next Generation Sequencing in Vision and Hearing Impairment |
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153 | (18) |
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153 | (2) |
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NGS Tests for Vision and Hearing Disorders |
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155 | (5) |
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Compatibility of Standard Enrichment Panels with Genetic Vision and Hearing Disorders |
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160 | (1) |
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Utility of NGS Testing for Diagnostic Purposes of Vision and Hearing Disorders |
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161 | (1) |
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162 | (1) |
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Digenic and Oligogenic Inheritance |
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162 | (1) |
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163 | (1) |
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163 | (1) |
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Novel Genes and "Erroneous" Disease Genes |
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164 | (1) |
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165 | (1) |
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166 | (1) |
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166 | (1) |
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166 | (5) |
Chapter 9 Next Generation Sequencing as a Tool for Noninvasive Prenatal Tests |
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171 | (18) |
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171 | (2) |
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Conventional Prenatal Diagnostics and Methods |
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173 | (1) |
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Use of Fetal Biological Material in the Maternal Circulation for Prenatal Diagnosis |
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173 | (1) |
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Fetal DNA in Prenatal Diagnosis |
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174 | (1) |
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Properties of Cell-Free Fetal DNA |
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174 | (2) |
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Applications of Noninvasive Prenatal Tests |
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176 | (3) |
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NGS in the Determination of Genomic Disorders by Using cffDNA in Maternal Plasma |
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179 | (1) |
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Single-Nucleotide Polymorphism Sequencing of Cell-Free Fetal DNA |
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180 | (2) |
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Limitations and Challenges of NGS-Based Noninvasive Prenatal Testing |
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182 | (1) |
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Clinical Implementation of Noninvasive Prenatal Testing for Aneuploidies |
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183 | (1) |
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184 | (1) |
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184 | (5) |
Chapter 10 Clinical Applications for Next Generation Sequencing in Cardiology |
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189 | (28) |
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189 | (3) |
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General Information on Multigene Panels |
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191 | (1) |
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192 | (7) |
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Hypertrophic Cardiomyopathy |
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195 | (1) |
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196 | (1) |
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Arrhythmogenic Right Ventricular Cardiomyopathy |
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197 | (1) |
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Restrictive Cardiomyopathy |
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198 | (1) |
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Left-Ventricular Noncompaction |
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198 | (1) |
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199 | (3) |
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199 | (1) |
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200 | (1) |
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Catecholaminergic Polymorphic Ventricular Tachycardia |
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200 | (1) |
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Cardiac Conduction Disease |
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201 | (1) |
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201 | (1) |
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202 | (1) |
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Thoracic Aortic Aneurysms and Dissections |
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202 | (2) |
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204 | (1) |
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Familial Hypercholesterolemia |
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205 | (1) |
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206 | (1) |
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List of Acronyms and Abbreviations |
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206 | (1) |
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207 | (1) |
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207 | (10) |
Chapter 11 Next Generation Sequencing in Pharmacogenomics |
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217 | (24) |
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217 | (1) |
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218 | (3) |
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Clinical Trials in Oncology |
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221 | (1) |
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Ethical Issues in Oncopharmacogenomics |
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222 | (1) |
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Multicenter Collaborations in Oncopharmacogenomics |
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222 | (2) |
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NGS in Noncancer Pharmacogenomics |
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224 | (1) |
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224 | (3) |
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Non-P450 Drug-Metabolizing Enzymes |
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227 | (1) |
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227 | (1) |
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Clinical Applications of Pharmacogenomics |
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228 | (2) |
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228 | (1) |
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229 | (1) |
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229 | (1) |
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229 | (1) |
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Anti-Human Immunodeficiency Virus Drugs |
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229 | (1) |
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Multigene Pharmacogenetic Tests Assessing Pharmacokinetics and Pharmacodynamics Response |
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230 | (1) |
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Quality Requirements for NGS-Based Pharmacogenomic Tests |
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231 | (2) |
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Guidelines for Clinical Application of Pharmacogenomics |
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233 | (1) |
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NGS in PharmacogenomicsOther Possible Applications |
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234 | (1) |
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Limitations of NGS in Pharmacogenomics |
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234 | (1) |
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235 | (1) |
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236 | (5) |
Chapter 12 The Role of Next Generation Sequencing in Genetic Counseling |
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241 | (18) |
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241 | (1) |
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242 | (2) |
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Genetic Counseling in the NGS Era |
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244 | (11) |
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Pretest Genetic Counseling |
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244 | (2) |
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246 | (2) |
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248 | (7) |
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255 | (1) |
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List of Acronyms and Abbreviations |
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256 | (1) |
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256 | (3) |
Chapter 13 Next Generation Sequencing in Undiagnosed Diseases |
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259 | (12) |
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259 | (1) |
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The Overall Genetic Testing Strategy in Undiagnosed DiseasesLooking for the Needle in a Haystack |
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260 | (2) |
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The Analysis of NGS Testing Results for Rare Diseases |
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262 | (1) |
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263 | (2) |
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Good Laboratory Practice in Genetic Testing for Undiagnosed Diseases |
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265 | (1) |
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265 | (1) |
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The Importance of Genetic Diagnosis in Rare Diseases |
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266 | (1) |
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267 | (1) |
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267 | (4) |
Chapter 14 Organizational and Financing Challenges |
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271 | (10) |
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275 | (1) |
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275 | (1) |
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276 | (1) |
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276 | (1) |
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277 | (1) |
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278 | (3) |
Chapter 15 Future Directions |
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281 | (14) |
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281 | (3) |
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282 | (1) |
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Emerging Commercial Solutions |
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283 | (1) |
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Future Directions of Clinical Genomics Data Processing |
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284 | (6) |
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Data Size Estimates and Current Processing Limitations |
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284 | (1) |
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285 | (1) |
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Hadoop Ecosystem Tools That Can Be Used in Genomic Medicine |
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286 | (2) |
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Data Security and Biobanking |
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288 | (1) |
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Currently Developing Scenarios and Cases |
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288 | (1) |
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Expected Challenges and Limitations of Future Data Processing Tools and Models |
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289 | (1) |
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Education of Physicians and Medical Researchers in the Understanding and Use of Genomic Data Processing |
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289 | (1) |
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Electronic Health Records |
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290 | (1) |
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ConclusionVision of Near-Future Medical Genomics Information Systems |
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291 | (1) |
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291 | (4) |
Chapter 16 Ethical and Psychosocial Issues in Whole-Genome Sequencing for Newborns |
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295 | (6) |
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295 | (2) |
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Differences between WGS and Genetic Testing in Other Contexts |
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297 | (2) |
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Newborn Metabolic Screening |
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297 | (1) |
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Carrier Testing in Carefully Selected High-Risk Populations |
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298 | (1) |
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Genetic Testing of Stored Samples in Biorepositories |
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298 | (1) |
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The Specific Ethical Issues of Whole-Genome Sequencing for Clinical Diagnosis |
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299 | (1) |
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Thinking about Harms and Benefits |
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299 | (1) |
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300 | (1) |
Chapter 17 Next Generation SequencingEthical and Social Issues |
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301 | (8) |
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Unpredictable Consequences of the Next Generation |
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Sequencing-Related Technological Revolution in Medical Genetics |
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301 | (1) |
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Problem 1: The Right Not to Know |
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302 | (1) |
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Problem 2: Incidental/Unsolicited Findings |
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303 | (1) |
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Problem 3: Genetic Determinism and Discrimination |
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304 | (1) |
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Problem 4: Genetically-Based Selection of Human Embryos and Assisted Reproductive Technology |
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304 | (1) |
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Problem 5: NGS and Social Issues |
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305 | (1) |
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306 | (1) |
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306 | (3) |
Index |
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