Clinical Molecular Diagnostics

✍ Scribed by Shiyang Pan, Jinhai Tang (ed.)

• Publisher: Springer
• Year: 2021
• Tongue: English
• Leaves: 888
• Category: Library

✦ Table of Contents

Foreword
Coordinators
Preface
Acknowledgments
Contents
About the Editors and Contributors
About the Editors
Editorial Board
Contributors
Part I: Principles of Clinical Molecular Diagnostics
1: Molecules of Disease and Their Detection Methods
1.1 Overview
1.2 Molecular Mechanism of Diseases
1.3 Nucleic Acid Detection Methods
1.3.1 Nucleic Acid Amplification Technology
1.3.2 Sequencing Technology
1.3.3 Nucleic Acid Hybridization Technology
1.3.4 Chip Technology
1.3.5 Biosensing Technology
1.4 Protein Detection Methods
1.4.1 Spectrum Technology
1.4.2 Protein Chip Technology
1.4.3 Labeled Immunoassay
1.4.4 Mass Spectrometric Technique
1.5 Future Trends
References
2: Assay Performance Evaluation
2.1 Precision
2.1.1 Terminology and Definitions
2.1.2 Overview of the Precision Evaluation Process (Fig. 2.1)
2.1.3 Features of the EP5-A2 Program
2.1.4 EP5-A2 Experimental Protocol and Requirements
2.1.4.1 Experimental Preparation
Experimental Sample
2.1.4.2 Experimental Method
2.1.4.3 Quality Control
2.1.5 Data Collection, Processing, and Statistical Analysis
2.1.5.1 Experimental Data Record
2.1.5.2 Outlier Test
2.1.5.3 Repeatability Estimate
2.2 Accuracy
2.2.1 Definitions
2.2.2 Features of the EP9-A2 Program
2.2.3 EP9-A2 Experimental Protocol and Requirements
2.2.3.1 Experimental Preparation
Sample Preparation
Comparison Method Selection
2.2.3.2 Experimental Method
2.2.3.3 Quality Control
2.2.4 Simple Accuracy Evaluation Plan
2.2.4.1 Comparison of Patient Sample Results to Those of Another Procedure
2.2.4.2 Method of Setting Reference Materials
Sources of Reference Materials
Procedure for Demonstration of Accuracy with Reference Materials
2.3 Sensitivity
2.3.1 Definitions
2.3.2 Discussion of Several Common Terms
2.3.3 Lower Limit of Linear Range (LLR), Biological Limit of Detection (BLD), and Functional Sensitivity (FS)
2.3.3.1 Lower Limit of Linear Range (LLR)
2.3.3.2 Biological Limit of Detection (BLD)
2.3.3.3 Functional Sensitivity (FS)
2.3.3.4 Experimental Precautions
Blank Sample
Detection Limit Sample
Time Required for the Experiment
2.3.4 Limits of Blank, Limits of Detection, and Limits of Quantitation
2.3.4.1 Overview
2.3.4.2 General Method for Determining the Limits of Blank (LoB)
2.4 Analytical Measurement Range
2.4.1 Definitions
2.4.2 EP6-A Protocol and Requirements
2.4.2.1 Experimental Requirements
Device Familiarization Period
Duration of the Experiment
Specimen of the Experiment
Number of Samples
Matrix Effects
Selection of Materials Used to Supplement Samples
Analyte Range
Sample Preparation and Value Assignment
2.4.2.2 Analytical Sequence
2.4.2.3 Preliminary Data Check
Outlier Inspection
Determination of the Linear Range
Degree of Nonlinearity
Considerations for Random Error
2.5 Variation Factors of Pre-analysis
2.5.1 Collection, Transport, and Preservation of Nucleic Acid Test Specimens
2.5.1.1 Preparation of Specimen Collection Site
2.5.1.2 Type and Collection of Specimens
2.5.1.3 Sampling and Transport Containers
2.5.1.4 Anti-pollution in Specimen Collection
2.5.1.5 Evaluation of Sampling Quality
References
3: Establishment of Biological Reference Interval
3.1 Biological Reference
3.1.1 Definitions and Terms
3.1.2 Clarifications
3.2 Establishment of Biological Reference Interval
3.2.1 Protocol Outline for Obtaining Reference Values and Establishing Reference Intervals
3.2.1.1 New Analyte or Analytical Method
3.2.1.2 Previously Measured Analyte
3.2.2 Selection of Reference Individuals
3.2.2.1 Exclusion Criteria
3.2.2.2 Partitioning Criteria
3.2.2.3 Selection of Reference Individuals
3.2.2.4 Sample Questionnaire
3.2.3 Pre-analytical and Analytical Considerations
3.2.4 Analysis of Reference Values
3.2.4.1 Minimum Number of Reference Values
3.2.4.2 Treatment of Outlying Observations
3.2.4.3 Partitioning of Reference Values
3.3 Verification of Biological Reference Interval
3.4 Description of Biological Reference Interval
3.4.1 Laboratory Presentation
3.4.2 Manufacturer Presentation
References
4: Ethics: Informed Consent, Patient Privacy
4.1 Overview
4.2 Informed Consent
4.2.1 Challenges
4.2.2 Regulations and Recommendations
4.2.3 What Should Be Included in the Informed Consent?
4.3 Patient Privacy and Confidentiality
4.3.1 Challenges
4.3.2 Regulations and Recommendations
4.3.3 How to Protect Patient Privacy?
4.4 Conclusion
References
5: Bioinformatics
5.1 Overview
5.1.1 Concept and Background
5.1.2 Research Categories
5.1.3 Common International Bioinformatics Centers
5.1.4 Common Bioinformatics Database
5.2 Biological Sequence Analysis
5.2.1 Sequence Analysis
5.2.2 Multiple Sequence Analysis
5.2.3 Molecular Polygenetic Tree
5.2.4 Comparative Genomics
5.3 Transcriptomics Data Analysis
5.3.1 Gene Expression Profile Analysis
5.3.2 Functional Enrichment Analysis
5.3.3 Timing Analysis
5.3.4 Gene Co-expression Network Analysis
5.3.5 Analysis of Transcriptional Regulation
5.4 Protein Structure Analysis
5.4.1 Protein Structure Prediction
5.4.2 Protein-Protein Interaction
5.4.3 Protein Function Prediction
5.5 Bioinformatics and Precision Medicine
5.5.1 Bioinformatics and Precision Medical Diagnosis
5.5.1.1 Genetic Testing
5.5.1.2 Detection of Pathogenic Microorganisms
5.5.2 Bioinformatics and Precision Medical Prevention and Treatment
5.5.3 Bioinformatics and the Future of Precision Medicine
References
6: Report and Consultation
6.1 Overview
6.2 Genetic Variation and Description
6.2.1 The Level of Sequence Variation
6.2.2 Content of the Variant Description
6.2.3 Types of Variant Sequences
6.2.4 Expression of Variant Types Specific Abbreviations Are Used to Describe Different Types of Sequence Variations
6.2.5 Reference Sequence
6.3 Naming Rules
6.3.1 Specific Rules for DNA Levels
6.3.2 Detailed Rules for RNA Levels
6.3.3 Detailed Rules of Protein Levels
6.3.3.1 Amino Acid Coding
6.3.3.2 Silent Changes
6.3.3.3 Substitutions, Missense Changes
6.3.3.4 Amino Acid Deletion
6.3.3.5 Frameshift Mutation
6.3.3.6 Amino Acid Insertion, Repeat
6.3.4 Gene Pharmacology Genotype Terminology
6.3.5 Other
6.4 Application of Gene Mutation in Disease Diagnosis
6.4.1 Genetic Variation and Genetic Diagnosis
6.4.2 Application of Genetic Variation Detection in Disease Diagnosis
6.4.2.1 Molecular Diagnosis of Mendelian Genetic Disease
6.4.2.2 Prenatal Diagnosis and Prenatal and Postnatal Care
6.4.2.3 Molecular Genetic Testing of Complex Diseases
6.4.2.4 Diagnosis and Treatment of Tumors
6.4.2.5 Detection of Pathogenic Microorganisms
6.5 What Is Involved Before the Clinical Report
6.5.1 Content Covered by the Clinical Report
6.5.1.1 The Test Report Should Include the Following
6.5.1.2 DNA Sequencing Reports and Explanations Should Include
6.5.1.3 Reports and Interpretations of Whole-Exon or Whole-Genome Next-Generation Sequencing Should also Include the Following
6.5.2 Clinical Interpretation of the Data
6.5.3 Clinical Molecular Diagnostic Testing Process and Precautions
6.5.3.1 Clinical Molecular Diagnostic Testing Process
6.5.3.2 Precautions for Clinical Reports
6.6 Reporting Model and Case Analysis
6.6.1 Tumor Molecular Diagnosis Report
6.6.1.1 Introduction to Non-small Cell Lung Cancer
6.6.1.2 Methods and Test Items for Clinical Molecular Diagnosis of Non-small Cell Lung Cancer
Source of NSCLC Target Molecule Detection Project
Detection Method of NSCLC Target Molecule
For Example
6.6.2 Molecular Diagnosis Report of Infectious Diseases
6.6.2.1 Introduction to Hepatitis B
6.6.2.2 Method and Test Item for Clinical Molecular Diagnosis of Hepatitis B Virus
Project Source
Detection Method
For Example
6.6.3 Noninvasive Prenatal Screening Results Report
6.6.3.1 Introduction to Noninvasive Prenatal Screening
6.6.3.2 Noninvasive Prenatal Screening Method and Test Project for Clinical Molecular Diagnosis
6.6.3.3 High Throughput Sequencing
For Example
6.6.4 Genetic Disease Diagnosis Report
6.6.4.1 Clinical Molecular Diagnosis of G6PD Deficiency
Introduction to G6PD Deficiency
Methods and Test Items for Clinical Molecular Diagnosis of G6PD Deficiency
Source of G6PD Deficiency Molecular Testing Project
For Example
References
7: Factors Associated with Variation
7.1 The Concept
7.2 Sampling
7.2.1 Specimen Collection
7.2.1.1 Time of Collection
7.2.1.2 Method of Collection
Body Position and Part in Blood Collection
Cuff
Infusion
7.2.1.3 Volume of Specimen
7.2.1.4 Precautions for Sample Collection
Collect Representative Specimens
Proper Use of Anticoagulant
Avoid Specimen Hemolysis and Container Contamination
Avoid Collecting Blood During Infusion
7.2.2 Sample Delivery and Preservation
7.2.2.1 Sample Delivery
Delivery Principle
Specially Assigned People
Receiving
7.2.2.2 Specimen Preservation
7.3 Biological Factors
7.3.1 Age
7.3.1.1 Neonatal
7.3.1.2 Children
7.3.1.3 The Elderly
7.3.2 Gender
7.3.3 Season
7.3.4 Altitude
7.3.5 Biological Cycle
7.3.6 Pregnancy
7.3.7 Lifestyle
7.4 Drugs
7.4.1 Interference of Drugs on Routine Inspection in Clinic
7.4.1.1 The Impact on Routine Blood Tests Results
7.4.1.2 The Impact on Routine Urine Test Results
7.4.1.3 The Impact on Routine Stool Test Results
7.4.2 Interference of Drugs on Clinical Biochemical Tests
7.4.2.1 Drugs Affecting Enzyme Assay
7.4.2.2 Drugs Affecting Blood Sugar Assay
7.4.2.3 Drugs Affecting Protein Assay
7.4.2.4 Drugs Affecting Lipid Assay
7.4.2.5 Drugs Affecting Electrolyte Assay
References
8: Quality Control and Quality Assurance
8.1 Overview
8.2 Laboratory Setting and Contamination Control
8.2.1 Laboratory Setting
8.2.2 Facilities
8.2.3 Laboratory Practices
8.2.4 Chemical and Enzymatic Controls
8.3 Internal Quality Control
8.3.1 Quantitative Tests
8.3.2 Qualitative Tests
8.4 Quality Assessments
8.4.1 Quality Indicators
8.4.2 External Quality Assessment
8.4.3 Auditing Program
8.5 Quality Control Material
8.6 Verification and Validation
8.7 The Process of Detection and Quality Control
8.7.1 Pre-analytic Phase
8.7.2 Analytic Phase
8.7.3 Post-analytical Phase
8.8 Personnel
8.9 Quality Control of Laboratory Equipment
8.10 Reagents and Consumables Quality Control
8.11 Quality Improvement
8.12 Document Control
8.13 Conclusion
References
9: Precision Medicine
9.1 Evidence-Based Laboratory Medicine
9.2 Translational Medicine of Molecular Diagnostic Tests
9.3 Molecular Diagnostic Tests in Personalized Medicine
9.4 The Application of Pharmacogenomics
9.5 Companion Diagnostics
References
Part II: Molecular Biomarkers and Signals from Diseased Functional Organ
10: Molecules in Body Systems
10.1 Overview
10.2 Four Major Families of Small Organic Molecules
10.2.1 Sugars Provide an Energy Source for Cells and Are the Subunits of Polysaccharides
10.2.2 Fatty Acids Are Precursors for Phospholipids and Other Membrane Components
10.2.3 Amino Acids Are the Subunits of Proteins
10.2.4 Nucleotides Are the Subunits of DNA and RNA
10.3 The Chemistry of Cells Is Dominated by Macromolecules with Remarkable Properties
10.3.1 Carbohydrates
10.3.2 Lipids
10.3.3 Nucleic Acids
10.3.4 Proteins
References
11: Molecules in Signal Pathways
11.1 Overview
11.2 Functions
11.2.1 The Change of Signal Transduction Molecules Is the Basis of Signal Transduction
11.2.1.1 Signal Transduction Molecules Constitute the Network of Signal Transduction Pathways
11.2.1.2 The Change in the Conformation and Activity of Signal Transduction Molecules Is the Basis of Signal Transduction
11.2.1.3 Changes of Intracellular Signal Transduction Molecule Content and Translocation Are Important Ways of Signal Transduction Regulation
11.2.2 Signal Transduction Molecules Are Important Targets for Drug Action
11.3 Signal Pathways
11.3.1 Apoptosis
11.3.1.1 The BCL-2 Family
11.3.1.2 Caspases
11.3.1.3 Inhibitors of Apoptotic Proteins
11.3.2 PI3K/AKT/mTOR Signal Pathway
11.3.2.1 Phosphatidylinositide 3 Kinase
11.3.2.2 Akt
11.3.2.3 Mammalian Target of Rapamycin
11.3.3 Wnt Signal Pathway
11.3.3.1 Wnt
11.3.3.2 Adenomatous Polyposis Coli
11.3.3.3 β-Catenin
11.3.3.4 c-Myc
11.3.4 Mitogen-Activated Protein Kinase Signal Pathway
11.3.4.1 Extracellular Signal-Regulated Kinase 1/2
11.3.4.2 c-Jun Terminal Kinases
11.3.4.3 p38
11.3.5 JAK/STAT Signal Pathway
11.3.5.1 JAKs
11.3.5.2 STATs
11.3.6 Angiogenesis
11.3.7 Notch Signal Pathway
11.4 Important Molecules
11.4.1 PD-1/PD-L1
11.4.2 HIF-1
11.4.3 p53
11.4.4 Tumor Specific Protein 70
References
12: Endocrine and Metabolism
12.1 Overview
12.2 Insulin
12.2.1 Sources and Characteristic
12.2.2 Methods
12.2.3 Reference Interval for Healthy Persons
12.2.4 Clinical Significance
12.2.4.1 The Application in the Diagnosis and Treatment of Diabetes
12.2.4.2 The Application in the Hypoglycemia Syndrome
12.2.4.3 The Application in the Diagnosis of Insulin Beta Cell Tumor
12.2.4.4 The Application of Other Diseases in the Diagnosis and Treatment
12.3 C-Peptide
12.3.1 Source and Characteristics
12.3.2 Methods
12.3.3 Reference Interval for Healthy Persons
12.3.4 Clinical Significance
12.4 Glycosylated Hemoglobin (HbA1c)
12.4.1 Sources and Characteristics
12.4.2 Methods
12.4.3 Reference Interval for Healthy Persons
12.4.4 Clinical Significance
12.4.5 Conclusions and Prospects
12.5 IGFBP-2
12.5.1 Sources and Characteristics
12.5.2 Methods
12.5.3 Reference Interval for Healthy Persons
12.5.4 Clinical Significance
12.5.5 Conclusions and Prospects
12.6 Thyroid Markers
12.6.1 The Function of Thyroid
12.6.2 Laboratory Evaluation of Thyroid
12.6.2.1 Tests That Asses the Hypothalamic-Pituitary-Thyroid Axis
T3 and T4
TSH and TRH
FT4 and FT3
12.6.2.2 Tests for Evaluation of Thyroid Autoimmunity
TG-Ab and TPO-Ab
TR-Ab
12.6.3 Conclusions and Prospects
12.7 Adrenal Gland Markers
12.7.1 Structure of Adrenal Gland
12.7.2 Function of Adrenal Gland
12.7.3 Laboratory Examination of Adrenal Gland
12.7.3.1 Tests That Assess the Level of Adrenal Medullary Hormone
12.7.3.2 Tests That Asses the Level of Adrenocortical Hormone
Examinations of Glucocorticoids and Their Metabolites in Blood, Urine, and Saliva
Examination of ATCH and N-POMC in Plasma
Dynamic Functional Test
Dexamethasone Inhibition Test
12.7.3.3 Genetic Testing
12.7.4 Conclusion
12.8 The Relevant Progress
References
13: Immune System
13.1 Overview
13.1.1 Autoimmune Diseases
13.1.2 Hypersensitive Diseases
13.1.2.1 Markers of Type I Hypersensitivity Diseases
13.1.2.2 Markers of Type II Hypersensitivity Diseases
13.1.2.3 Markers of Type III Hypersensitivity Diseases
13.1.2.4 Markers of Type IV Hypersensitivity Diseases
13.2 Tissue-specific Autoantibodies
13.2.1 Anti-intrinsic Factor Antibody (AIFA)
13.2.2 Anti-parietal Cell Antibody
13.2.3 Anti-smooth Muscle Antibody
13.2.4 Anti-liver/Kidney Microsome Antibody
13.2.5 Anti-pituitary Antibody
13.2.6 Anti-thyroid Antibody
13.2.7 Anti-glutamic Acid Decarboxylase Antibody
13.2.8 Anti-islet Cell Antibody
13.2.9 Anti-insulin Antibody
13.2.10 Anti-adrenocortical Antibody
13.2.11 Anti-glomerular Basement Membrane Antibody
13.3 Systemic Autoantibodies
13.3.1 Anti-mitochondrial Antibody
13.3.2 Human Anti-globulin Antibody
13.3.3 Anti-cold Agglutinin Antibody
13.3.4 Anti-nuclear Antibody
13.3.5 Anti-extractable Nuclear Antibody
13.3.5.1 Anti-Smith Antibody
13.3.5.2 Anti-SSA/Ro Antibody and Anti-SSB/La Antibody
13.3.5.3 Anti-RNP Antibody
13.3.5.4 Anti-topoisomerase Antibody (ATA)/Anti-Scl-70 Antibody
13.3.6 Anti-cardiolipin Antibody
13.3.7 Anti-DNA Antibody
13.3.7.1 Anti-dsDNA Antibody
13.3.7.2 Anti-ssDNA Antibody
13.3.8 Anti-histone Antibody
13.3.9 Anti-centromere Antibody
13.3.10 Anti-p62 Antibody (AP62A)/Anti-sp100 Antibody/Anti-glycoprotein-210 Antibody (AGPA, Anti-gp210, Anti-nup210, Anti-np210)
13.3.11 Rheumatoid Factor
13.3.12 Anti-citrullinated Peptide Antibody (Anti-CCP Antibody)
13.3.13 Anti-glucose-6-Phosphate Isomerase (Anti-G6PI)
13.3.14 Antineutrophil Cytoplasmic Antibody
13.3.15 Rh Antibody
13.3.16 Anti-erythrocyte Antibody
13.3.17 Anti-HLA Antibody
13.3.18 Prospects for Autoantibodies
13.4 Immunoglobulin E
13.5 Relevant Activated Cell Markers
13.5.1 Mast Cells
13.5.2 Eosinophil Activation Marker
13.5.3 The Activation Markers of Basophil and Neutrophil
13.5.4 T Lymphocyte Immunophenotype
13.6 Complement System
13.7 Circulation Immune Complex
13.8 Other Markers
13.8.1 Cytokines
13.8.2 Proteins and Enzymes
13.9 The Relevant Progress
References
14: Lipoproteins
14.1 Overview
14.1.1 Basic Concepts
14.1.2 Functions and Metabolic Pathways of Various Lipoproteins
14.1.2.1 Chylomicrons Transport Exogenous Triglycerides and Cholesterol
14.1.2.2 Very Low-Density Lipoproteins Transport Endogenous Triglycerides
14.1.2.3 Low-Density Lipoprotein Transports Endogenous Cholesterol
14.1.2.4 High-Density Lipoprotein Transports Cholesterol in Reverse Fashion
14.1.3 Lipoprotein Metabolic Disturbances
14.1.3.1 Hyperlipoproteinemia
Primary Hyperlipoproteinemia
Hyperlipoproteinemia
Secondary Hyperlipoproteinemia
Clinical Manifestations of Hyperlipoproteinemia
Diagnostic Criteria for Hyperlipoproteinemia
14.1.3.2 Hypolipoproteinemia
14.1.3.3 Lipoprotein Metabolic Disturbance and Atherosis
Factors Leading to Atherosis
Lipoprotein Remnants
Modified LDL
Type B LDL
LP(a)
14.2 Total Cholesterol
14.2.1 Sources and Characteristics
14.2.2 Detection Methods and Reference Values of Healthy People
14.2.2.1 Detection Methods
14.2.2.2 Reference Values of Healthy Individuals
14.2.2.3 Clinical Significance
14.2.2.4 Related Progress
14.3 Triglycerides
14.3.1 Sources and Characteristics
14.3.2 Detection Methods and Reference Values of Healthy Individuals
14.3.2.1 Detection Methods
14.3.2.2 Reference Values of Healthy Individuals
14.3.2.3 Clinical Significance
14.3.2.4 Related Progress
14.4 Free Fatty Acids
14.4.1 Sources and Characteristics
14.4.2 Detection Methods and Reference Values of Healthy Individuals
14.4.2.1 Detection Methods
14.4.2.2 Reference Values of Healthy Individuals
14.4.2.3 Clinical Significance
14.5 Phospholipids
14.5.1 Sources and Characteristics
14.5.2 Detection Methods and Reference Values of Healthy People
14.5.2.1 Detection Methods
14.5.2.2 Reference Values of Healthy Individuals
14.5.2.3 Clinical Significance
14.6 Lipoprotein
14.6.1 High-Density Lipoprotein
14.6.1.1 Sources and Characteristics
14.6.1.2 Detection Methods and Reference Values of Healthy Individuals
Detection Methods
14.6.1.3 Reference Values of Healthy Individuals
14.6.1.4 Clinical Significance
14.6.1.5 Related Progress
14.6.2 Low-Density Lipoprotein
14.6.2.1 Sources and Characteristics
14.6.2.2 Detection Methods and Reference Values of Healthy Individuals
Detection Methods
Reference Values of Healthy Individuals
14.6.2.3 Clinical Significance
14.6.2.4 Related Progress
14.6.3 Small and Dense Low-Density Lipoprotein
14.6.3.1 Sources and Characteristics
14.6.3.2 Detection Methods and Reference Values of Healthy Individuals
Detection Methods
Reference Values of Healthy Individuals
14.6.3.3 Clinical Significance
14.6.3.4 Related Progress
14.6.4 Lipoprotein (a)
14.6.4.1 Sources and Characteristics
14.6.4.2 Detection Methods and Reference Values of Healthy Individuals
Detection Methods
Reference Values of Healthy Individuals
14.6.4.3 Clinical Significance
14.6.4.4 Related Progress
References
15: Transport and Carrier Proteins
15.1 Overview
15.2 Apolipoprotein AI (AI, ApoAI)
15.2.1 Sources and Characteristics
15.2.2 Detection Methods and Reference Values of Healthy Individuals
15.2.2.1 Detection Methods
15.2.2.2 Reference Values of Healthy Individuals
15.2.3 Clinical Significance
15.2.4 Related Progression
15.3 Apolipoprotein B
15.3.1 Sources and Characteristics
15.3.2 Detection Methods and Reference Values of Healthy Individuals
15.3.2.1 Detection Methods
15.3.2.2 Reference Values of Healthy Individuals
15.3.3 Clinical Significance
15.3.4 Related Progress
15.4 Apolipoprotein B/Apolipoprotein AI Ratio (ApoB/ApoAI Ratio)
15.4.1 Sources and Characteristics
15.4.2 Detection Methods and Reference Values of Healthy Individuals
15.4.2.1 Detection Methods
15.4.2.2 Reference Values of Healthy Individuals
15.4.3 Clinical Significance
15.4.4 Related Progress
15.5 Apolipoprotein CII and CIII
15.5.1 Sources and Characteristics
15.5.2 Detection Methods and Reference Values of Healthy Individuals
15.5.2.1 Detection Method
15.5.2.2 Reference Values of Healthy Individuals
15.5.3 Clinical Significance
15.5.4 Related Progress
15.6 Apolipoprotein E
15.6.1 Sources and Characteristics
15.6.2 Detection Methods and Reference Values of Healthy Individuals
15.6.2.1 Detection Methods
15.6.2.2 Reference Values of Healthy Individuals
15.6.3 Clinical Significance
15.6.4 Related Progress
15.7 Apolipoprotein H
15.7.1 Sources and Characteristics
15.7.2 Detection Methods
15.7.2.1 Detection Methods
15.7.2.2 Reference Value of Healthy Individuals
15.7.3 Clinical Significance
15.7.4 Research Progress
15.8 Apolipoprotein M
15.8.1 Sources and Characteristics
15.8.2 Detection Methods and Reference Values of Healthy Individuals
15.8.2.1 Detection Methods
15.8.2.2 Reference Values of Healthy Individuals
15.8.3 Clinical Significance
15.8.4 Research Progress
References
16: Coagulation and Fibrinolysis
16.1 Overview
16.2 Fibrinogen
16.2.1 Sources and Characteristics
16.2.2 Detection Method and Reference Range
16.2.3 Clinical Significance
16.3 D-Dimer
16.3.1 Sources and Characteristics
16.3.2 Detection Method
16.3.3 Healthy Person Reference Range
16.3.4 Clinical Significance
16.4 Fibrinogen/Fibrin Degradation Product
16.4.1 Sources and Characteristics
16.4.2 Detection Method
16.4.3 Healthy Person Reference Range
16.4.4 Clinical Significance
16.5 Protein C
16.5.1 Sources and Characteristics
16.5.2 Detection Method
16.5.3 Healthy Person Reference Range
16.5.4 Clinical Significance
16.6 Protein S
16.6.1 Sources and Characteristics
16.6.2 Detection Method
16.6.3 Healthy Person Reference Range
16.6.4 Clinical Significance
16.7 Antithrombin
16.7.1 Sources and Characteristics
16.7.2 Detection Method
16.7.3 Healthy Person Reference Range
16.7.4 Clinical Significance
16.8 Plasminogen
16.8.1 Sources and Characteristics
16.8.2 Detection Method
16.8.3 Healthy Person Reference Range
16.8.4 Clinical Significance
16.9 α2-Plasmin Inhibitor
16.9.1 Sources and Characteristics
16.9.2 Detection Method
16.9.3 Healthy Person Reference Range
16.9.4 Clinical Significance
16.10 Von Willebrand Factor
16.10.1 Sources and Characteristics
16.10.2 Detection Method
16.10.3 Healthy Person Reference Range
16.10.4 Clinical Significance
16.11 Thrombomodulin
16.11.1 Sources and Characteristics
16.11.2 Detection Method and Healthy Person Reference Range
16.11.3 Clinical Significance
16.12 Plasminogen Activator Inhibitor Type 1
16.12.1 Sources and Characteristics
16.12.2 Detection Method
16.12.3 Healthy Person Reference Range
16.12.4 Clinical Significance
16.13 Tissue Factor Pathway Inhibitor
16.13.1 Sources and Characteristics
16.13.2 Detection Method
16.13.3 Healthy Person Reference Range
16.13.4 Clinical Significance
16.14 Laboratory Tests for Clotting Factor Deficiency Screening
16.14.1 Prothrombin Time
16.14.1.1 Sources and Characteristics
16.14.1.2 Detection Method
16.14.1.3 Healthy Person Reference Range
16.14.1.4 Clinical Significance
16.14.2 Activated Partial Thromboplastin Time
16.14.2.1 Sources and Characteristics
16.14.2.2 Detection Method
16.14.2.3 Healthy Person Reference Range
16.14.2.4 Clinical Significance
16.14.3 Thrombin Time
16.14.3.1 Sources and Characteristics
16.14.3.2 Detection Method
16.14.3.3 Healthy Person Reference Range
16.14.3.4 Clinical Significance
16.14.4 Coagulation Factor Assay
16.14.4.1 Sources and Characteristics
16.14.4.2 Detection Method
16.14.4.3 Healthy Person Reference Range
16.14.4.4 Clinical Significance
16.15 Molecular Diagnosis of Inherited Bleeding Disorders
16.15.1 Molecular Diagnosis of Hemophilia A and Hemophilia B
16.15.2 Molecular Diagnosis of Von Willebrand Disease
16.15.3 Molecular Diagnosis of Rare Bleeding Disorders
16.16 Related Progress
References
17: Cardiovascular System
17.1 Overview
17.2 Myocardial Damage Markers
17.2.1 Cardiac Troponin (cTn)
17.2.2 Myoglobin (Mb)
17.2.3 Creatine Kinase Isoenzyme MB (CK-MB)
17.2.4 Heart Type-Fatty Acid Binding Protein (H-FABP)
17.2.5 Copeptin
17.3 Myocardial Ischemia Markers
17.3.1 Ischemic Modified Albumin (IMA)
17.4 Heart Function Markers
17.4.1 Brain Natriuretic Peptide (BNP) or NT-proBNP
17.4.2 Soluble Suppression of Tumorigenicity-2 (sST2)
17.4.3 Adrenomedullin (ADM)
17.5 Inflammatory Markers
17.5.1 C-Reactive Protein (CRP)
17.5.2 Interleukin-6 (IL-6)
17.6 Markers That Predict Heart-Risk Events
17.6.1 Homocysteine (Hcy)
17.6.2 Lipoprotein-Associated Phospholipase A2 (Lp-PLA2)
17.6.3 Myeloperoxidase (MPO)
17.7 Other Markers
17.7.1 MicroRNAs
17.7.2 KCNQ1
17.7.3 SCN5A
17.7.4 RYR2
17.7.5 KCNE1
17.7.6 KCNH2
References
18: Pregnancy
18.1 Overview
18.2 Human Chorionic Gonadotropin (hCG)
18.2.1 Resource and Characteristics
18.2.2 Detection Methods
18.2.3 Reference Range
18.2.4 Clinical Application
18.2.4.1 Diagnosis and Monitor Normal/Abnormal Pregnancy
18.2.4.2 Diagnosis of Gestational Trophoblastic Disease (GTD)
18.2.4.3 Marker for Down’s Syndrome Screening
18.3 Alpha-Fetoprotein (AFP)
18.3.1 Resource and Characteristics
18.3.2 Detection Methods
18.3.3 Reference Range
18.3.4 Clinical Applications
18.3.4.1 Prenatal Diagnosis
18.3.4.2 Diagnosis and Monitoring of Hepatocellular Carcinoma and Other Germ Cell Tumors
18.4 Pregnancy-Associated Plasma Protein-A (PAPP-A)
18.4.1 Resource and Characteristics
18.4.2 Detection Methods
18.4.3 Reference Range
18.4.4 Clinical Applications
18.5 Inhibin
18.5.1 Resource and Characteristics
18.5.2 Detection Methods
18.5.3 Reference Range
18.5.4 Clinical Application
18.5.4.1 A Marker of Trophoblast Viability and Placental Dysfunction
18.5.4.2 Prenatal Serum Screening for Down’s Syndrome
18.5.4.3 Prenatal Serum Screening for Other Chromosome Abnormalities
18.5.4.4 A Marker to Evaluate the Development of Hypertensive Disorders of Pregnancy
18.6 Unconjugated Estriol
18.6.1 Resource and Characteristics
18.6.2 Detection Method
18.6.3 Reference Range
18.6.4 Clinical Application
18.6.4.1 Prenatal Serum Screening for Down’s Syndrome
18.6.4.2 Monitor Placental Function and Fetal Development
18.7 Cell-Free DNA (cfDNA)
18.7.1 Resource and Characteristics
18.7.2 Detection Method
18.7.3 Clinical Application
18.7.3.1 Trisomy 21 (Down’s Syndrome)
18.7.3.2 Trisomy 18 (Edwards Syndrome)
18.7.3.3 Trisomy 13
References
19: Urine
19.1 Overview
19.2 Urea
19.2.1 Sources and Characteristics
19.2.2 Detection Methods
19.2.3 Normal Reference Interval
19.2.4 Clinical Significance
19.3 Creatinine
19.3.1 Sources and Characteristics
19.3.2 Detection Methods
19.3.3 Normal Reference Interval
19.3.4 Clinical Significance
19.4 Urinary Microalbumin
19.4.1 Sources and Characteristics
19.4.2 Detection Methods
19.4.3 Normal Reference Interval
19.4.4 Clinical Significance
19.5 Cystatin C
19.5.1 Sources and Characteristics
19.5.2 Detection Methods
19.5.3 Normal Reference Interval
19.5.4 Clinical Significance
19.6 Transferrin
19.6.1 Sources and Characteristics
19.6.2 Detection Methods
19.6.3 Normal Reference Interval
19.6.4 Clinical Significance
19.7 Uric Acid
19.7.1 Sources and Characteristics
19.7.2 Detection Methods
19.7.3 Normal Reference Interval
19.7.4 Clinical Significance
19.8 α1-Microglobulin
19.8.1 Sources and Characteristics
19.8.2 Detection Methods
19.8.3 Normal Reference Interval
19.8.4 Clinical Significance
19.9 β2-Microglobulin
19.9.1 Sources and Characteristics
19.9.2 Detection Methods
19.9.3 Normal Reference Interval
19.9.4 Clinical Significance
19.10 Neutrophil Gelatinase-Associated Lipocalin
19.10.1 Sources and Characteristics
19.10.2 Detection Methods
19.10.3 Normal Reference Interval
19.10.4 Clinical Significance
19.11 N-Acetyl-β-d Glucosamine Glycosaminase
19.11.1 Sources and Characteristics
19.11.2 Detection Methods
19.11.3 Normal Reference Interval
19.11.4 Clinical Significance
19.12 Retinol Binding Protein
19.12.1 Sources and Characteristics
19.12.2 Detection Methods
19.12.3 Normal Reference Interval
19.12.4 Clinical Significance
References
20: Bone
20.1 Overview
20.2 BAP
20.2.1 Sources and Characteristics
20.2.2 Methods
20.2.3 Reference Interval for Healthy Persons
20.2.4 Clinical Significance
20.2.5 Conclusions and Prospects
20.3 N-MID Osteocalcin
20.3.1 Sources and Characteristics
20.3.2 Methods
20.3.3 Reference Interval for Healthy Persons
20.3.4 Clinical Significance
20.3.5 Conclusions and Prospects
20.4 Total PINP
20.4.1 Sources and Characteristics
20.4.2 Methods
20.4.3 Reference Interval for Healthy Persons
20.4.4 Clinical Significance
20.4.5 Conclusions and Prospects
20.5 PINP
20.5.1 Sources and Characteristics
20.5.2 Methods
20.5.3 Reference Interval for Healthy Persons
20.5.4 Clinical Significance
20.5.5 Conclusions and Prospects
20.6 PICP
20.6.1 Sources and Characteristics
20.6.2 Methods
20.6.3 Reference Interval for Healthy Persons
20.6.4 Clinical Significance
20.6.5 Conclusions and Prospects
20.7 β-Crosslaps
20.7.1 Sources and Characteristics
20.7.2 Methods
20.7.3 Reference Interval for Healthy Persons
20.7.4 Clinical Significance
20.8 Conclusions and Prospects
References
21: Cancer
21.1 Overview
21.1.1 The Ideal Biomarker for Cancer
21.1.2 Classification of Tumor Biomarkers
21.1.2.1 Classification by Biochemical Properties
21.1.2.2 Classification by Sources
21.1.2.3 Classification by Oncogenesis and Development of Tumors
21.2 Tumor Markers with Different Biochemical Properties
21.2.1 Oncofetal Protein
21.2.1.1 AFP
21.2.1.2 AFP-L3
21.2.1.3 CEA
21.2.2 Protein
21.2.2.1 TPA and TPS
21.2.2.2 CYFRA21-1
21.2.2.3 PIVKA-II
21.2.3 Enzymes
21.2.3.1 PSA
21.2.3.2 NSE
21.2.3.3 LDH
21.2.4 Sugar Esters or Glycoproteins
21.2.4.1 CA125
21.2.4.2 CA15–3
21.2.4.3 CA19–9
21.2.5 Hormone
21.2.5.1 HCG
21.2.5.2 CA
21.3 Multistage Biomarkers of Tumorigenesis and Development
21.3.1 Molecular Biomarkers for Early Diagnosis
21.3.1.1 SPLUNC1
21.3.1.2 APC
21.3.1.3 RASSF1A
21.3.1.4 EBERs
21.3.1.5 DAPK
21.3.1.6 NES1
21.3.1.7 DCC
21.3.2 Molecular Biomarkers for Invasion and Metastasis
21.3.2.1 Adhesion Molecules
E-Cadherins
Integrins
CD44
21.3.2.2 Proteolytic Enzymes and Their Inhibitors
MMP
uPA
Cathepsin
21.3.2.3 Tumor Microangiogenesis-Related Molecules
Promoting Microangiogenesis Factors
VEGF
MVD
Inhibitory Microangiogenesis Factors
Angiostatin and Endostatin
21.3.2.4 Autocrine Motility Factor
AMF
Gp78
21.3.3 Molecular Biomarkers for Prognosis
21.3.3.1 Survivin
21.3.3.2 Cyclin D1
21.3.3.3 P53
21.3.3.4 TSLC1
21.3.3.5 BAG-1
21.3.3.6 Bmi-1
21.4 Molecular Biomarkers for Precision Medicine
21.4.1 Breast Cancer
21.4.1.1 HER2
21.4.1.2 ER and PR
21.4.1.3 BRCA1/BRCA2
21.4.2 Lung Cancer
21.4.2.1 EGFR
21.4.2.2 ALK
21.4.2.3 ROS-1
21.4.3 Colorectal Cancer
21.4.3.1 CIN
21.4.3.2 MSI
21.4.3.3 CIMP
21.5 Novel Molecular Biomarkers of Tumor
21.5.1 Tumor Specific Protein 70 (SP70)
21.5.1.1 Sources and Characteristics
21.5.1.2 Clinical Detection Methods
21.5.1.3 Clinical Application
21.5.2 CTC
21.5.3 ctDNA
21.5.4 DNA Methylation in Peripheral Blood
21.5.5 Circulating miRNAs
21.5.6 LncRNA
21.5.7 CircRNA
21.5.8 Exosome
21.5.9 Endosome
21.6 Future Prospects for Cancer Biomarkers
References
22: Translation Research of Novel Biomarker
22.1 Overview
22.2 Discovery
22.2.1 Characteristics of Molecular Biomarkers
22.2.2 Biomarker Classification and Samples
22.2.3 Existing Detection Techniques for Clinical Application
22.2.4 Biomarker Discovery Approaches
22.2.4.1 Strategy of Biomarker Discovery
Research Subjects
Omics Technologies
22.2.4.2 Biomarker Function Identification
Role Transformation of P53
Current Novel Tumor Biomarkers
Pro-Gastrin-Releasing Peptide (ProGRP)
Protein Induced by Vitamin K Absence/Antagonist-II (PIVKA-II)
22.2.5 Artificial Intelligence and Big Data
22.2.6 Monoclonal Antibody Library Technique
22.2.6.1 Usage of Monoclonal Antibody Library
Research on Diagnostic Tumor Biomarker
Cancer Target Therapy
Advantages of the Monoclonal Antibody Library
22.2.7 Transformation Determinants
22.3 Qualification and Verification
22.3.1 Samples from Clinical Cohort
22.3.2 Platforms for Qualification/Verification
22.3.2.1 Enzyme-Linked Immunosorbent Assay (ELISA)
22.3.2.2 Mass Spectrometry
22.3.2.3 Selection of Assays
22.4 Assay Optimization
22.4.1 Development of Clinical Diagnostic Monoclonal Antibodies
22.4.2 Preanalytical Variation
22.4.2.1 Sample Collection and Processing
22.4.2.2 Physiological Factors
22.4.3 Analytical Evaluation
22.4.3.1 Indicators of Accuracy
22.4.3.2 Indicators of Precision
22.4.3.3 Analytical Measurement Range (AMR)
22.4.4 Reference Intervals
22.4.5 Cut-off Value
22.5 Clinical Evaluation
22.6 Progress
References
Part III: Advanced Molecular Diagnostic Techniques
23: Next-Generation Sequencing (NGS)
23.1 Overview
23.2 Basic Principle
23.2.1 Library Construction Principle and Characteristics
23.2.1.1 Construction of DNA Library
23.2.1.2 Construction of RNA Library
23.2.2 High-Throughput Sequencing Principles and Features
23.2.2.1 Illumina Sequencing
23.2.2.2 Ion Torrent Semiconductor Sequencing
23.2.2.3 Complete Genomics Sequencing Platform
23.2.2.4 Single-Molecule Sequencing
23.3 Technology Development
23.3.1 Summary of Technology Development
23.3.2 First-Generation Sequencing Technology
23.3.2.1 Maxam-Gilbert Chemical Degradation Sequencing
23.3.2.2 Deoxygenation Chain Termination Sequencing
23.3.2.3 DNA Automated Sequencing
23.3.3 Next-Generation Sequencing
23.3.3.1 Pyrosequencing
23.3.3.2 454/Roche Sequencing System
23.3.3.3 Ion Torrent/Life Technologies Sequencing System
23.3.3.4 Solexa/Illumina Sequencing System
23.3.3.5 SOLiD/Life Technologies Sequencing System
23.3.3.6 Complete Genomics/BGI Sequencing System
23.3.4 Third Generation of Sequencing Technology
23.3.4.1 Pacific Bioscience SMRT Sequencing Technology
23.3.4.2 Oxford Nanopore Technologies Nanopore Sequencing Technology
23.3.5 Development and Prospect of Sequencing Technology
23.4 Clinical Application
23.4.1 Application of NGS in Noninvasive Prenatal Screening for Chromosome Aneuploidy
23.4.2 Application of NGS in Preimplantation Genetic Screening
23.4.3 Application of NGS in the Detection of Single-Gene Genetic Diseases
23.4.4 Application in the Detection of Tumors
23.4.5 Application of NGS in Tumor-Targeted Therapy
23.4.6 Application of NGS in the Detection of Pathogenic Microorganisms
23.4.7 Application of NGS in Epigenetic Detection
23.4.8 Application of NGS in Sequencing of Immune Repertoire (IR)
23.4.9 Application of NGS in Transcriptomics
References
24: Digital PCR
24.1 Overview
24.2 Basic Principle
24.2.1 Statistics and Quantitative Principles of Digital PCR
24.2.1.1 Confidence Interval in Absolute Quantification
24.2.2 Experimental Principle of Digital PCR
24.2.3 Technology Development
24.2.3.1 The Germination of Digital PCR
24.2.3.2 Proposal of Digital PCR Concept
24.2.3.3 BEAMing Digital PCR
24.2.3.4 Microfluidic Digital PCR
24.2.4 Clinical Application
24.2.4.1 Application Characteristics of Digital PCR
24.2.4.2 Application of Digital PCR on Genomics
24.2.4.3 Application of Digital PCR on Translational Medicine and Precision Medicine
Individualized Medicine and Liquid Biopsy Technique
Application of Digital PCR on Drug Resistance Surveillance
Prenatal Examination
24.2.4.4 Application of Digital PCR on Food Safety
24.2.4.5 Application of Digital PCR on Environmental Microorganisms
24.2.4.6 Other Applications on Digital PCR
Quality Control of Sequencing Library and Verification of Sequencing Result
Gene Editing
24.2.4.7 The Trend of Development of Digital PCR
References
25: Biosensor
25.1 Overview
25.1.1 Characteristics
25.1.1.1 Low Cost and High Speed
25.1.1.2 High Precision and Stability
25.1.1.3 High Specificities
25.1.1.4 Wide Range of Applications
25.1.1.5 Simple Operation and Automatic Analysis
25.1.2 Classifications
25.2 Basic Principle
25.2.1 Principles of Electrochemical Biosensor
25.2.1.1 Electrochemical Immunosensor
25.2.1.2 Electrochemical Enzyme Electrode Sensor
25.2.1.3 Electrochemical DNA Sensor
25.2.1.4 Electrochemical Cell Sensor
25.2.1.5 Cell Receptor-Based Cell Sensor
25.2.1.6 Cellular Lesion-Based Cell Sensor
25.2.1.7 Cell Sensor Integrating Optical Measurement Technology and Electronic Measurement Technology
25.2.2 Principles of Optical Biosensor
25.2.2.1 Passive Optical Sensor
25.2.2.2 Photoinduced Optical Biosensor
25.2.2.3 Electro-optical Biosensor
25.2.3 Principles of Piezoelectric Biosensor
25.3 Technology Development
25.3.1 Wearable Biosensor
25.3.2 Molecular Biosensor and Imaging
25.3.3 Biological Function Simulation Sensor
25.3.3.1 Odor Sensor
25.3.3.2 Taste Sensor
25.3.4 Biosensor Chips
25.4 Clinical Application
References
26: Microfluidic Chip
26.1 Overview
26.2 Basic Principle
26.2.1 Separation
26.2.2 Detection
26.3 Technology Development
26.3.1 Silica and Glass
26.3.2 Polymers
26.3.3 Hydrogel
26.3.4 Paper
26.3.5 Droplet
26.4 Clinical Application
26.4.1 Capillary Electrophoresis
26.4.2 Detection of Nucleic Acid
26.4.2.1 Polymerase Chain Reaction
26.4.2.2 Detection of Gene Mutation
26.4.2.3 Genotyping Detection
26.4.2.4 DNA Sequencing
26.4.3 Amino Acid Analysis
26.4.4 Peptide and Protein Analysis
26.4.4.1 Sample Manipulation and Detection
26.4.4.2 Protein-Ligand Interaction Analysis
26.4.4.3 Mass Spectrometry-Based Proteomics
26.4.5 Immunoassay
26.4.6 Cell Culture and Analysis
26.4.6.1 Cell Manipulation
26.4.6.2 Cell Culture and Cell-to-Cell Interaction Analysis
26.4.6.3 Single-Cell Analysis
26.4.7 Drug Assay and Screening
26.4.7.1 Drug Delivery System
26.4.7.2 Drug Screening
26.4.8 Enzymatic Analysis
26.4.9 Mono-molecular Detection
References
27: Liquid Biopsy
27.1 Overview
27.2 Basic Principle
27.2.1 Circulating Tumor DNA
27.2.1.1 Sample Collection and DNA Extraction
27.2.1.2 ctDNA Detection
PCR-Based Gene Analysis
Sequencing-Based Gene Mutation Analysis
Whole Genome Sequencing Analysis
27.2.2 Circulating Tumor Cells
27.2.2.1 CTC Detection Technologies Without Enrichment
27.2.2.2 CTC Detection Technologies with Enrichment
Molecular Marker-Based Cell Enrichment
Negative Enrichment
Positive Enrichment
Physical Property and Non-affinity-Based Microfluidic Cell Enrichment
27.2.3 Exosomes
27.2.3.1 Isolation
27.2.3.2 Analysis of Exosomes
27.3 Technology Development
27.3.1 Circulating Tumor DNA
27.3.1.1 PCR-Based Techniques
27.3.1.2 Sequencing Techniques
NGS in Liquid Biopsy
27.3.2 Circulating Tumor Cells
27.3.2.1 CellSearch System
27.3.2.2 MagSweeper
27.3.2.3 ISET
27.3.2.4 MEMS
27.3.2.5 FMSA
27.3.2.6 Vortex
27.3.2.7 SP70-Targeted Tumor Cell Enrichment
27.3.2.8 SP70-Targeted Flow Cytometry
27.3.3 Exosomes
27.3.3.1 Isolation of Exosomes
Ultracentrifugation Techniques
Size-Based Techniques
Immunoaffinity Capture-Based Techniques
Precipitation
Microfluidic-Based Isolation Techniques
27.3.3.2 Analysis of Exosomes
Physical Analysis
Chemical, Biochemical, and Compositional Analysis
27.4 Clinical Application
27.4.1 Circulating Tumor DNA
27.4.2 CTCs
27.4.3 Exosome
27.4.4 Comparison Between CTCs, ctDNA, and Exosome Tests in Cancer Detection
27.4.5 Challenges and Outlook
References
28: Molecular-Targeted Imaging
28.1 Overview
28.2 Basic Principle
28.2.1 Probes
28.2.2 Molecular-Targeted Imaging Strategy
28.2.3 Molecular-Targeted Imaging Type
28.3 Technology Development
28.3.1 PET/CT
28.3.2 SPECT
28.3.3 PET/MR
28.3.4 CT
28.3.5 Ultrasound
28.3.6 Optical Imaging
28.4 Clinical Application
28.4.1 Cancer
28.4.2 Cardiovascular Diseases
28.4.3 Central Nervous System Diseases
28.4.4 Autoimmune Diseases
28.4.5 Drug Development
References
29: Fluorescence In Situ Hybridization
29.1 Overview
29.2 Basic Principle
29.2.1 Preparation of the Slides
29.2.2 Preparation of the Probes
29.2.3 Fluorescence In Situ Hybridization
29.2.4 FISH Quality Control
29.3 Technology Development
29.3.1 Immuno-FISH
29.3.2 Multiplex-FISH (M-FISH), Spectral Karyotyping (SKY) and RxFISH
29.3.3 RNA-FISH
29.3.4 Three-Dimensional FISH (3D-FISH)
29.3.5 Fiber-FISH
29.3.6 CGH (Comparative Genomic Hybridization)
29.3.7 Array-CGH
29.3.8 Flow-FISH
29.4 Clinical Application
29.4.1 Prenatal Diagnosis
29.4.2 Hematopoietic Diseases and Lymphoma Related Tests
29.4.3 Application of FISH in Pathogen Detection
29.4.4 FISH for Detection of Circulating Tumor Cells (CTC)
29.4.5 Application of FISH in Solid Oncology
References
30: Circulating DNA Quantification
30.1 Overview
30.2 Basic Principle
30.2.1 Sample Selection of Circulating DNA Testing
30.2.2 Isolation of Circulating DNA
30.2.3 Analysis Platform of Circulating DNA
30.2.3.1 Massive Parallel Sequencing
30.2.3.2 Quantitative Polymerase Chain Reaction, PCR
30.3 Technology Development
30.3.1 Duplex Real-Time PCR for Total Plasma DNA Quantitation
30.3.2 Candidate Gene Approach
30.3.2.1 Allele-Specific PCR (AS PCR)
30.3.2.2 Competitive Allele-Specific TaqMan PCR (CAST PCR)
30.3.2.3 Coamplification at Lower Denaturation Temperature PCR (COLD-PCR)
30.3.2.4 Peptide Nucleic Acid-Locked Nucleic Acid PCR (PNA-LNA PCR)
30.3.2.5 Droplet Digital PCR (ddPCR)
30.3.2.6 Microfluidic Digital PCR
30.3.2.7 “Beads, Emulsion, Amplification, Magnetics Digital PCR” (BEAMing)
30.3.3 Whole-Genome Sequencing Methods
30.3.4 Targeted Deep Sequencing
30.3.4.1 Tagged AMplicon Deep Sequencing (TAM-Seq)
30.3.4.2 Safe-Sequencing System (Safe-SeqS)
30.3.4.3 Duplex Sequencing
30.3.4.4 Cancer Personalized Profiling by Deep Sequencing (CAPP-Seq)
30.4 Clinical Application
30.4.1 Prognostic Value
30.4.2 Diagnosis Value
30.4.3 Detecting Resistance Mechanisms
30.4.4 Detecting Minimal Residual Disease
30.4.5 Noninvasive Prenatal Testing (NIPT)
30.4.6 Injury Assessment
References
31: DNA Methylation Detection Techniques
31.1 Overview
31.2 Basic Principle
31.2.1 DNA Enrichment Methods
31.2.2 ChIP-Seq
31.2.3 Mapping Open Chromatin
31.2.4 Chromosome Conformation Capture
31.3 Technology Development
31.3.1 Genome-Wide Methylation Analysis
31.3.1.1 High-performance Liquid Chromatography
31.3.1.2 High-performance Capillary Electrophoresis
31.3.2 Methylation Detection of Specific Sites
31.3.2.1 Bisulfite Sequencing (BSP)
31.3.2.2 Methylation Specificity PCR
31.3.2.3 Methylight
31.3.2.4 High-resolution Melting (HRM)
31.3.2.5 Combined Bisulfite Restriction Analysis (COBRA)
31.3.2.6 Pyrosequencing
31.3.2.7 Analysis of DNA Methylation Map Based on Chip
31.3.2.8 Single Molecule Real-Time (SMRT) Sequencing Technology
31.3.2.9 Flight Mass Spectrometry
31.4 Clinical Application
References
Part IV: Disease Presentation and Clinical Laboratory Procedures
32: Immunological Disorders
32.1 Allergic Disease
32.1.1 Overview
32.1.2 Pathogenesis
32.1.2.1 Immune Cells in Allergy
32.1.2.2 Inflammatory Molecules in Allergy
32.1.3 Atopic Dermatitis
32.1.3.1 Overview
32.1.3.2 Clinical Appearance
32.1.3.3 Laboratory Diagnosis
Serum Total IgE
Detection of Eosinophils in Peripheral Blood
Serum Eosinophil Cationic Protein (ECP)
Allergen Skin Patch Test or Prick Test
Basophil Activation Test (BAT)
32.1.4 Allergic Asthma
32.1.4.1 Overview
32.1.4.2 Clinical Appearance
32.1.4.3 Laboratory Diagnosis
Allergic Skin Prick Test and Serum IgE Test
Induced Sputum Test
Fractional Exhaled Nitric Oxide (FeNO) Measurement
BAT
Gene Detection
32.1.5 Allergic Rhinitis
32.1.5.1 Overview
32.1.5.2 Clinical Appearance
32.1.5.3 Laboratory Diagnosis
Supportive Methods for the Diagnosis of AR Include Skin Prick Test (SPT) and Serum Specific IgE
Inhalation Allergen Screening Test (Phadiatop)
ECP Detection
32.1.6 Food Allergy
32.1.6.1 Overview
32.1.6.2 Clinical Appearance
IgE-Mediated Food Allergy
Non-lgE-Mediated Food Allergy
Mixed IgE and Non-IgE-Related Food Allergies
Laboratory Diagnosis
Component Resolution Diagnosis (CRD)
Gene Detection
32.1.7 Drug Allergy
32.1.7.1 Overview
32.1.7.2 Clinical Appearance
32.1.7.3 Laboratory Diagnosis
General Laboratory Examination
Gene Detection
32.1.8 Typical Medical Case
32.2 Autoimmune Diseases
32.2.1 Overview
32.2.1.1 Classification of Autoimmune Diseases
32.2.1.2 Common Characteristics of Autoimmune Diseases
32.2.1.3 Pathogenesis of Autoimmune Diseases (Fig. 32.2)
32.2.1.4 The Appearance of Autoantigens
32.2.1.5 Abnormal Immune Regulation
32.2.1.6 Abnormal Expression of Fas/FasL
32.2.1.7 Genetic Factors
32.2.2 The Mechanism of Immune Injury in Autoimmune Diseases (Fig. 32.3)
32.2.2.1 Type II Hypersensitivity
32.2.2.2 Type III Hypersensitivity
32.2.2.3 Type IV Hypersensitivity
32.2.3 Common Autoimmune Diseases
32.2.3.1 Autoimmune Hemolytic Anemia (AIHA)
Case 1, Primary WAIHA
32.2.3.2 Immune Thrombocytopenic Purpura (ITP)
32.2.3.3 Systemic Lupus Erythematosus (SLE)
Experimental Diagnosis of SLE
Case 2, SLE
32.2.3.4 Rheumatoid Arthritis (RA)
Case 3, RA
32.2.3.5 Sjögren’s Syndrome (SS)
32.2.3.6 Myasthenia Gravis (MG)
32.2.3.7 Pulmonary Hemorrhagic Nephritis Syndrome
32.2.4 Major Immunological Detection of Autoimmune Diseases
32.2.4.1 Detection of Autoantibodies and Its Clinical Significance
Systemic Lupus Erythematosus (SLE)
Rheumatoid Arthritis (RA): Detection of Autoantibodies to RA
Autoimmune Hemolytic Anemia
Sjögren’s Syndrome (SS)
32.2.4.2 Clinical Significance of Immunoglobulin and Complement Examination
32.2.4.3 Lymphocyte Detection
32.2.4.4 Detection of Cytokines
32.2.4.5 Application Principles of Immunoassay for Autoimmune Diseases
32.3 Acquired Immune Deficiency Syndrome
32.3.1 Overview
32.3.1.1 HIV Morphology
32.3.1.2 HIV Gene Structure
32.3.1.3 Virus Characteristics
32.3.1.4 Route of Transmission of AIDS
32.3.2 Clinical Appearance
32.3.2.1 General Symptoms
32.3.2.2 Respiratory Symptoms
32.3.2.3 Digestive Symptoms
32.3.2.4 Nervous System Symptoms
32.3.2.5 Skin and Mucous Membrane Damage
32.3.2.6 Tumor
32.3.3 Detection Method
32.3.3.1 Antibody Detection
Screening Test
Confirmatory Reagent
32.3.3.2 Antigen Detection
32.3.3.3 Nucleic Acid Detection
Qualitative Detection
Quantitative Detection
32.3.3.4 CD4+ and CD8+ T Lymphocyte Detection
32.3.3.5 Virus Isolation and Culture
32.3.3.6 HIV-1 Genotype Resistance Detection
32.3.4 Therapy
32.3.4.1 General Treatment
32.3.4.2 Antiviral Therapy
32.3.4.3 Drug Resistance
References
33: Liver Diseases
33.1 Viral Hepatitis
33.1.1 Overview
33.1.2 Hepatitis A
33.1.2.1 Overview
33.1.2.2 Clinical Appearance
33.1.2.3 Laboratory Diagnosis
Immunological Detection
Molecular Biological Detection
Nucleic Acid Molecular Hybridization
RT-PCR
33.1.2.4 Management
33.1.2.5 Typical Medical Case
33.1.3 Hepatitis B
33.1.3.1 Overview
33.1.3.2 Clinical Appearance
33.1.3.3 Laboratory Diagnosis
Immunological Detection
HBsAg
Anti-HBs Antibodies
HBeAg
Anti-HBe Antibodies
HBcAg
Anti-HBc Antibodies
Molecular Biological Detection
Quantitative Analysis of HBV DNA
Quantitative Analysis of HBV RNA
HBV Typing
Analysis of Drug Resistance of HBV
33.1.3.4 Management
33.1.3.5 Typical Medical Case
33.1.4 Hepatitis C
33.1.4.1 Overview
33.1.4.2 Clinical Appearance
33.1.4.3 Laboratory Diagnosis
Immunological Detection
Screening Test
Confirmatory
Molecular Biological Detection
Detection of HCV Nucleic Acid
Genotyping of HCV
33.1.4.4 Management
33.1.4.5 Typical Medical Case
Results with Interpretation Guideline
Final Diagnosis
33.1.5 Hepatitis D
33.1.5.1 Overview
33.1.5.2 Clinical Appearance
Co-Infection
Superinfection
33.1.5.3 Laboratory Diagnosis
Immunological Detection
Molecular Biological Detection
33.1.5.4 Management
33.1.6 Hepatitis E
33.1.6.1 Overview
33.1.6.2 Clinical Appearance
33.1.6.3 Laboratory Diagnosis
33.1.6.4 Management
33.1.6.5 Typical Medical Case
Final Diagnosis
33.2 Autoimmune Hepatitis
33.2.1 Overview
33.2.2 Clinical Appearance
33.2.3 Laboratory Diagnosis
33.2.3.1 Serum Biochemical Indicators
33.2.3.2 Autoantibody
ANA
Anti-Smooth Muscle Antibodies (ASMA)
Anti-Liver/Kidney Microsomal Antibodies (ALKM)
Anti-Liver Cytosol Type 1 (LC-1) Antibodies
Antibodies Against Soluble Liver Antigens/Antibodies Against Liver Pancreas (SLA/LP)
33.2.3.3 Serum Immunoglobulin
33.2.3.4 Histopathology
33.2.3.5 Conclusion
33.3 Hepatocellular Carcinoma
33.3.1 Overview
33.3.2 Surveillance and Diagnosis
33.3.2.1 Surveillance
33.3.2.2 Diagnosis
33.3.3 Biomarkers
33.3.3.1 Alpha-Fetoprotein (AFP)
33.3.3.2 Glypican-3 (GPC3)
33.3.3.3 Golgi Protein-73 (GP73)
33.3.3.4 Alpha-l-Fucosidase (AFU)
33.3.3.5 Protein Induced by Vitamin K Absence/Antagonist-II (PIVKA-II)
33.3.3.6 Squamous Cell Carcinoma Antigen (SCCA)
33.3.3.7 MicroRNAs
33.3.3.8 Other Biomarkers
Tumor Specific Protein 70 (SP70)
Long Non-coding RNAs (LncRNAs)
Circular RNAs (CircRNAs)
Contents in Exosome
33.3.4 Genetic Variations
33.3.5 Treatment
33.3.6 Typical Medical Case
33.4 Wilson Disease
33.4.1 Clinical Appearance
33.4.1.1 Clinical Manifestations
33.4.1.2 Neurological and Psychiatric Manifestations
33.4.1.3 Ophthalmic Manifestations
33.4.2 Diagnosis
33.4.2.1 Liver Function Tests
33.4.2.2 Biochemical Investigations
Ceruloplasmin
Total Serum Copper
Urinary Copper Excretion
33.4.2.3 Liver Biopsy and Liver Copper Content
33.4.2.4 Imaging
33.4.2.5 Genetic Testing
33.4.3 Correlation Between Phenotype and Genotype
33.4.4 Genetic Counselling
33.4.5 Prenatal Diagnosis and Preimplantation Genetic Diagnosis
33.4.6 Typical Clinical Case
References
34: Pancreatic Diseases
34.1 Pancreatic Ductal Adenocarcinoma
34.1.1 Overview
34.1.2 Clinical Appearance
34.1.3 Laboratory Diagnosis
34.1.3.1 Mucin Tumor Markers
CA19-9
CA50
CA242
DU-PAN-2
CAM17.1/Wheat-Germ Agglutinin (WGA)
34.1.3.2 Other Markers
Tumor-Specific Protein (SP70)
Carcinoembryonic Antigen
Membrane Antigens
PAM4
MicroRNAs
34.1.3.3 Proteomics
34.1.3.4 Genetic Testing
34.1.4 Management
34.1.5 Treatment
34.1.6 Typical Medical Case
34.2 Chronic Pancreatitis
34.2.1 Overview
34.2.2 Clinical Appearance
34.2.3 Laboratory Diagnosis
34.2.3.1 Exocrine Pancreatic Enzymes or Hormones
34.2.3.2 Human Pancreatic Polypeptide (PP)
34.2.3.3 Pancreatic Function Tests
Indirect Pancreatic Function Tests
Direct Pancreatic Function Tests
34.2.3.4 Genetic Testing
34.2.4 Management
34.2.5 Treatment
34.2.6 Typical Medical Case
34.3 Insulinoma
34.3.1 Overview
34.3.2 Clinical Appearance
34.3.3 Laboratory Diagnosis
34.3.3.1 C-Peptide Inhibition Test with Hog Insulin
34.3.3.2 Intravenous Secretin Test for Insulinoma
34.3.3.3 The 72-h Fast Test
34.3.3.4 Genetic Testing
34.3.4 Management
34.3.5 Treatment
34.4 Intraductal Papillary Mucinous Neoplasms
34.4.1 Overview
34.4.2 Clinical Appearance
34.4.3 Laboratory Diagnosis
34.4.3.1 Mucin Tumor Markers and Oncofetal Antigens
CEA
CA19-9
34.4.3.2 Other Tumor Markers
CF protein
S100 Protein
mAb Das-1
MicroRNAs
34.4.3.3 Genetic Testing
34.4.4 Management
34.4.5 Typical Medical Case
References
35: Digestive Tract Disease
35.1 Gastritis
35.1.1 Classification
35.1.1.1 Based on the Course of Disease
35.1.1.2 Based on Etiology
Helicobacter pylori Gastritis
Chemical Gastritis
Autoimmune Gastritis
35.1.2 Clinical Manifestation
35.1.3 Laboratory Diagnosis
35.1.3.1 Endoscopy
35.1.3.2 Histology
35.1.3.3 Helicobacter pylori
35.1.4 Biomarker
35.1.4.1 Pepsinogens
35.1.4.2 Gastrin 17
35.1.4.3 HOX Transcript Antisense RNA
35.1.5 Typical Medical Case
35.2 Diarrhea
35.2.1 Overview
35.2.2 Acute Diarrhea
35.2.2.1 Infections
35.2.2.2 Poisoning
35.2.2.3 Medications
35.2.2.4 Other Diseases
35.2.3 Chronic Diarrhea
35.2.4 Laboratory Examination
35.2.4.1 Stool Tests
Fecal Bacterial Culture
Stool Routine
Detection of Virus, Virus Antigen, and Virus Nucleic Acid in Feces
35.2.4.2 Blood Tests
35.2.4.3 Serological Tests
35.2.4.4 Others Tests
35.2.5 Biomarkers
35.2.5.1 Calprotectin
35.2.5.2 Lactoferrin
35.2.5.3 Anti-Saccharomyces cerevisiae Antibodies (ASCA)
35.2.5.4 Antineutrophil Cytoplasmic Antibody (ANCAs)
35.2.5.5 C-Reactive Protein (CRP)
35.2.5.6 Anti-Vinculin and Anti-Cytolethal Distending Toxin B Antibodies (CdtB)
35.2.5.7 Angiotensin-Converting Enzyme 2 (ACE 2)
35.2.6 Conclusion
35.2.7 Typical Medical Case
35.3 Crohn’s Disease
35.3.1 Overview
35.3.2 Clinical Manifestation
35.3.3 Laboratory Diagnosis
35.3.3.1 CRP and ESR
35.3.3.2 Hematologic Tests
35.3.3.3 Fecal Calprotectin and Other Fecal Marker
35.3.3.4 Other Serological Markers
35.3.3.5 Microbiology
35.3.3.6 Genetic Testing
35.3.3.7 Endoscopy
35.3.3.8 Imaging
35.3.4 Conclusions
35.3.5 Typical Medical Case
35.4 Esophageal Cancer
35.4.1 Overview
35.4.2 Epidemiology
35.4.3 Etiology
35.4.3.1 Squamous Cell Carcinoma
35.4.3.2 Adenocarcinoma
35.4.4 Screening
35.4.5 Clinical Diagnosis
35.4.6 Molecular Diagnosis
35.4.6.1 Genetic and Epigenetic Alterations Detection and Its Implications
35.4.6.2 Molecular Diagnosis of Micrometastasis and CTCs
35.4.6.3 miRNA-Based Molecular Diagnosis
35.4.6.4 Genetic Polymorphism
35.4.6.5 Novel Molecular Markers
ADAMTS16
Tumor Specific Protein (SP70)
35.4.7 Therapy
35.4.7.1 Ablation
35.4.7.2 Cryotherapy
35.4.7.3 Endoscopic Mucosal Resection
35.4.7.4 Esophagectomy
35.4.8 Treatment Modalities Used in Locally Advanced Esophageal Cancer
35.4.8.1 Radiation Therapy
35.4.8.2 Chemotherapy
35.4.8.3 Chemoradiation Alone
35.4.8.4 Chemoradiation and Surgery
35.4.8.5 Surveillance
35.4.8.6 Palliative Options for Esophageal Carcinoma
35.4.9 Molecules of Companion Diagnosis
35.4.9.1 Targeting the EGFR Signaling Pathway
35.4.9.2 Targeting the HER2 Signaling Pathway
35.4.9.3 Angiogenesis Inhibitors
35.4.9.4 Others
35.4.10 Typical Medical Case
35.5 Gastric Cancer
35.5.1 Overview
35.5.2 Clinical Appearance
35.5.3 Risk Factors for Gastric Cancer
35.5.4 Historical Classification of GC
35.5.5 Laboratory Diagnosis
35.5.5.1 Principles of Biomarker Testing by NCCN Guidelines for GC
35.5.5.2 Traditional Biomarkers of GC
35.5.5.3 Molecular Biomarkers of GC
Tumor Specific Protein 70 (SP70)
HER2/neu
MSI
PD-L1
Circulating Nucleic Acids
The Other Genetic Susceptibility Genes
35.5.6 Typical Medical Case
35.5.7 Conclusion
35.6 Colorectal Cancer
35.6.1 Overview
35.6.2 Epidemiology
35.6.3 Aetiology
35.6.3.1 Environmental Factors
35.6.3.2 Genetic Factors
35.6.3.3 Other Risk Factors
Colorectal Polyps (Adenomatous Polyps)
Inflammatory Bowel Disease
Cholecystectomy
35.6.4 Screening
35.6.4.1 Screening Object
35.6.4.2 Screening Test
Questionnaire Survey Based on High-Risk Factors
Fecal Occult Blood Test (FOBT)
Fecal DNA Testing
Endoscopy
35.6.5 Clinical Diagnosis
35.6.5.1 Clinical Manifestation
Changes in Bowel Habits and Fecal Traits
Abdominal Pain
Abdominal Mass
35.6.5.2 Digital Rectal Examination
35.6.5.3 Imaging Examination
35.6.5.4 Histopathology
35.6.6 Molecular Diagnosis
35.6.6.1 Broad-Spectrum Tumor Serum Markers
CEA
CA19-9
CA242 and CA50
35.6.6.2 Tumor Specific Protein (SP70)
35.6.6.3 Liquid Biopsy
CTCs
CfDNA
35.6.6.4 Genetic Biomarkers
Microsatellite Instability (MSI)
KRAS and BRAF Mutations
SMAD4 Mutation
35.6.6.5 Proteomics
P53
CDX2
MutT-Related Proteins
C-Met
35.6.6.6 Epigenetics
MicroRNA (miRNA)
Methylation
CpG island Methylator Phenotype (CIMP)
ZNF331
LINE-1
35.6.7 Therapy
35.6.8 Typical Medical Case
References
36: Kidney Diseases
36.1 Polycystic Kidney Disease
36.1.1 Overview
36.1.2 Diagnosis
36.1.3 Genetic Testing Algorithm
36.1.4 Correlation Between Phenotype and Genotype
36.1.5 Genetic Counselling
36.1.6 Prenatal Diagnosis and Preimplantation Genetic Diagnosis
36.1.7 Typical Clinical Case
36.2 Nephropathy
36.2.1 Overview
36.2.2 Classification
36.2.2.1 Glomerular Diseases
Acute Glomerulonephritis
Signs and Symptoms
Causes and Pathogenesis
Molecular Markers
Serum Glomerular Filtration Markers
Urinary Glomerular Cell Injury Markers
Treatment
Chronic Glomerulonephritis
Signs and Symptoms
Causes and Pathogenesis
Molecular Markers
Treatment
Nephrotic Syndrome
Signs and Symptoms
Causes
Pathogenesis
Complications
Laboratory Diagnosis
Treatment
IgA Nephropathy
Signs and Symptoms
Causes
Pathogenesis
Laboratory Diagnosis
Treatment
36.2.2.2 Tubular Injury
Signs and Symptoms
Causes and Pathogenesis
Molecular Markers
36.3 Kidney Cancer
36.3.1 Overview
36.3.1.1 Summary of Renal Tumors
36.3.1.2 The Classification of Malignant Kidney Diseases
36.3.2 Renal Cell Carcinoma
36.3.2.1 Serological Markers of Renal Cell Carcinoma
Traditional Biomarkers for Renal Cell Carcinoma
Novel Molecular Markers for Renal Cell Carcinoma
Transforming Growth Factor β (TGF-β)
Carbonic Anhydrase IX
PTEN
B7-H1
Insulin-Like Growth Factor II mRNA Binding Protein 3 (IMP3)
Other Laboratory Diagnostic Testings
36.3.2.2 Typical Case
36.3.3 Renal Pelvis Carcinoma
36.3.3.1 Biomarkers of Renal Pelvic Carcinoma
Traditional Biomarkers for Renal Pelvic Carcinoma
β2 Microglobulin
Neuro-Specific Enolase
Novel Molecular Biomarkers for Renal Pelvic Carcinoma
Oncogene Marker
Tamm–Horsfall Protein Antibody
36.3.3.2 Typical Case
36.4 Hantavirus Hemorrhagic Fever with Renal Syndrome
36.4.1 Overview
36.4.2 Pathogenesis
36.4.2.1 Pathogenesis
Direct Action of the Virus
Immunity
The Role of Various Cytokines and Mediators
36.4.2.2 Pathology and Physiology
Shock
Bleeding
Acute Renal Failure
36.4.3 Course of Disease
36.4.3.1 Fever Period
36.4.3.2 Hypotension Shock Period
36.4.3.3 Oliguria
36.4.3.4 Polyuria
36.4.3.5 Recovery Period
36.4.4 Diagnosis
36.4.4.1 Blood Routine
36.4.4.2 Urine Routine
36.4.4.3 Biochemical Tests
36.4.4.4 Special Inspections
36.4.4.5 Other Auxiliary Inspections
36.4.4.6 Differential Diagnosis
36.4.5 Treatment
36.4.6 Typical Medical Case
References
37: Cardiovascular Disease
37.1 Acute Myocardial Infarction
37.1.1 Overview
37.1.2 Clinical Appearance
37.1.3 Laboratory Diagnosis
37.1.4 Management
37.1.5 Conclusion
37.2 Heart Failure
37.2.1 Overview
37.2.2 Clinical Appearance
37.2.3 Laboratory Diagnosis
37.2.4 Management
37.2.5 Conclusion
37.3 Myocarditis
37.3.1 Overview
37.3.2 Clinical Appearance
37.3.3 Laboratory Diagnosis
37.3.3.1 Endomyocardial Biopsy
37.3.3.2 Cardiac Biomarkers
37.3.3.3 Inflammation Biomarkers
37.3.3.4 Pathogenetic Diagnosis
37.3.4 Management
37.3.5 Conclusion
37.4 Congenital Heart Disease (CHD)
37.4.1 Overview
37.4.2 Clinical Appearance
37.4.2.1 Excessive Sweating
37.4.2.2 Poor Feeding
37.4.2.3 Acyanotic and Cyanotic Congenital Heart Diseases
37.4.2.4 Heart Murmurs
37.4.3 Laboratory Diagnosis
37.4.3.1 Karyotyping
37.4.3.2 Array CGH
37.4.3.3 Whole-Exome Sequencing
37.4.3.4 Whole-Genome Sequencing
37.4.4 Management
37.4.5 Conclusion
37.5 Arrhythmia
37.5.1 Overview
37.5.2 Clinical Appearance
37.5.3 Laboratory Diagnosis
37.5.3.1 LQTS
37.5.3.2 SQTS
37.5.3.3 Brugada Syndrome
37.5.3.4 Catecholaminergic Polymorphic Ventricular Tachycardia
37.5.4 Management
37.5.5 Conclusion
References
38: Lung Disease
38.1 Lung Cancer
38.1.1 Overview
38.1.2 Etiology and Pathogenesis
38.1.3 Clinical Appearance
38.1.4 Routine Diagnosis (Fig. 38.3)
38.1.4.1 Imaging Tests
Chest X-Ray
CT Scan
Magnetic Resonance Imaging
38.1.4.2 Endoscopic and Histopathological Examination
Sputum Cytology
Bronchoscopy
Mediastinoscopy
Needle Biopsy
38.1.5 Molecular Diagnosis
38.1.5.1 Routine Biomarkers
38.1.5.2 Companion Diagnostic Biomarker (Fig. 38.5) (Table 38.1)
EGFR
ALK and ROS1
KRAS
BRAF
MET
HER2
PD-1/PD-L1
Others
38.1.5.3 Other Biomarkers
Tumor Specific Protein 70
Auxiliary Diagnosis
Therapy Efficacy Monitoring
Predict Prognosis
DNA Methylation
Potential Biomarkers
38.1.5.4 Liquid Biopsy
38.1.6 Treatments and Therapies
38.1.7 Conclusion
38.1.8 Typical Medical Case
38.2 Cystic Fibrosis
38.2.1 Overview
38.2.2 Clinical Appearance
38.2.2.1 Respiratory System
38.2.2.2 Digestive System
38.2.2.3 Other
38.2.3 Laboratory Diagnosis
38.2.4 Conclusion
38.3 Pneumonia
38.3.1 Overview
38.3.2 Clinical Appearance
38.3.3 Laboratory Diagnosis
38.3.3.1 Pathogenic Diagnosis
38.3.3.2 Key Points for the Laboratory Diagnosis of Respiratory Infections
38.3.4 Management
38.3.5 Conclusion
38.4 Tuberculosis
38.4.1 Overview
38.4.2 Clinical Appearance
38.4.3 Laboratory Diagnosis
38.4.4 Typical Medical Case
38.4.5 Management
38.4.6 Conclusion
38.5 Influenza
38.5.1 Overview
38.5.2 Pathogenesis
38.5.2.1 Transmission
38.5.2.2 Pathology and physiology
38.5.3 Epidemiology
38.5.3.1 Seasonal Variations
38.5.3.2 Epidemic and Pandemic Spread
38.5.4 Course of the Disease
38.5.5 Diagnosis
38.5.5.1 Virus Isolation and Identification
38.5.5.2 Serological Testing and Typing Methods
38.5.5.3 Quick Diagnosis
Loop-Mediated Isothermal Amplification
Gene Chip Technology
Pyrosequencing Technology
Nuclear Acid Sequence-Based Amplification
38.5.6 Prevention and Treatment
38.5.6.1 Prevention
Influenza Vaccination
Improve Your Own Immunity
Other
38.5.6.2 Treatment
NA Inhibitors
M2 Inhibitors
38.5.7 Typical Medical Case
38.6 COVID-19
38.6.1 Overview
38.6.2 Pathogenesis
38.6.2.1 Transmission
38.6.2.2 Pathology and Physiology
38.6.3 Epidemic and Pandemic Spread
38.6.4 Course of the Disease
38.6.4.1 Clinical Classification
38.6.5 Diagnosis
38.6.5.1 Blood Routine and Biochemical Indicators
38.6.5.2 Serological Detection of 2019-nCoV
38.6.5.3 Molecular Diagnostic Methods
Specimen Collection and Storage
Biosafety Considerations
Detection of 2019-nCoV by Real-Time RT-PCR
Assay Control Addition
Interpretation of Results
Detection of 2019-nCoV by Genetic Sequencing
38.6.5.4 Chest CT for COVID-19
38.6.5.5 Clinically Diagnosis
38.6.6 Prevention and Treatment
38.6.6.1 Prevention
Diagnosis and Isolation
Improve Your Immunity
Others
38.6.6.2 Treatment
38.6.7 Typical Medical Case
References
39: Blood Disorders
39.1 Blood Cancer
39.1.1 Overview
39.1.2 Myeloid Neoplasms
39.1.2.1 Myelodysplastic Syndromes
39.1.2.2 Acute Myeloid Leukemia
39.1.2.3 Chronic Myeloid Leukemia
39.1.2.4 Myeloproliferative Neoplasms
39.1.2.5 Myelodysplastic/Myeloproliferative Neoplasms
39.1.3 Lymphoid Neoplasms
39.1.3.1 Lymphoid Leukemia
39.1.3.2 Lymphoma
39.1.3.3 Myeloma
39.1.4 Conclusion
39.2 Coagulation Disorders
39.2.1 Hemophilia
39.2.1.1 Introduction
Hemophilia A
Mutations in the F8 Gene
Hemophilia B
Mutations in the F9 Gene
39.2.1.2 Clinical Manifestation
39.2.1.3 Laboratory Diagnosis
Hemophilia A
Hemophilia B
39.2.1.4 Management
39.2.1.5 Conclusions
39.2.2 Von Willebrand Disease
39.2.2.1 Introduction
Molecular Basis of Disease
Type 1 Von Willebrand Disease
Type 3 Von Willebrand Disease
Type 2 Von Willebrand Disease
Type 2A Von Willebrand Disease
Type 2B Von Willebrand Disease
Type 2M Von Willebrand Disease
Type 2N (Normandy) Von Willebrand Disease
39.2.2.2 Clinical Manifestation
39.2.2.3 Laboratory Diagnosis
39.2.2.4 Management
39.2.2.5 Conclusions
39.2.3 Hereditary Thrombocytopenia
39.2.4 Typical Medical Case
39.3 Hematologic Disorders
39.3.1 Hemoglobinopathies
39.3.1.1 Sickle Cell Disease
Overview
Clinical Manifestation
Laboratory Diagnosis
Management
Conclusions
39.3.2 Thalassemia
39.3.2.1 Overview
α-Thalassemia
β-Thalassemia
39.3.2.2 Clinical Manifestation
39.3.2.3 Laboratory Diagnosis
39.3.2.4 Management
39.3.2.5 Conclusions
39.3.3 Typical Medical Case
References
40: Endocrine and Metabolic Diseases
40.1 Diabetes
40.1.1 Overview
40.1.2 Classification and Clinical Appearance
40.1.2.1 Categories of Increased Risk for Diabetes (Prediabetes)
40.1.2.2 Type 1 Diabetes Mellitus
40.1.2.3 Type 2 Diabetes Mellitus
40.1.2.4 Gestational Diabetes Mellitus
40.1.2.5 Monogenic Diabetes Syndromes
40.1.3 Diagnosis
40.1.3.1 Prediabetes
40.1.3.2 Diagnostic Criteria for Diabetes Mellitus
40.1.3.3 Gestational Diabetes Mellitus
40.1.3.4 Monogenic Diabetes
40.1.4 Laboratory Diagnosis
40.1.4.1 Blood Glucose
40.1.4.2 Urinary Glucose
40.1.4.3 Glucose Tolerance Test
40.1.4.4 Glycated Hemoglobin (HbA1c)
40.1.4.5 Ketone Body
40.1.4.6 Lactic Acid and Pyruvic Acid
40.1.4.7 Blood Glucose Regulator
40.1.4.8 Urinary Microalbumin
40.1.4.9 Genetic Test
40.1.4.10 Autoimmune Markers
40.1.4.11 Other
40.1.5 Management
40.1.6 Conclusion
40.1.7 Typical Medical Case
40.2 Thyroid Disease
40.2.1 Overview
40.2.2 Thyroid Carcinoma
40.2.2.1 Classification of Thyroid Carcinoma
40.2.2.2 Differentiated Thyroid Carcinoma
40.2.2.3 Medullary Thyroid Carcinoma
40.2.2.4 Typical Case
40.2.3 Nontoxic Goiter
40.2.3.1 Etiology and Epidemiology
40.2.3.2 Classification of Goiter
40.2.3.3 Laboratory Diagnosis of Nontoxic Goiter
40.2.3.4 Typical Case
40.2.4 Thyroid Nodule
40.2.4.1 Definition and Clinical Manifestations
40.2.4.2 Laboratory Diagnosis
40.2.4.3 Typical Case
40.2.5 Thyroiditis
40.2.5.1 Introduction
40.2.5.2 Classification and Laboratory Diagnosis of Thyroiditis
40.2.5.3 Typical Case
40.2.6 Hypothyroidism
40.2.6.1 Definition and Classification of Hypothyroidism
40.2.6.2 Diagnosis of Hypothyroidism
40.2.6.3 Typical Case
40.2.7 Hyperthyroidism and Thyrotoxicosis
40.2.7.1 Graves’ Disease
40.2.7.2 Toxic Adenoma and Multinodular Toxic Goiter
40.2.7.3 Typical Case
40.3 Dwarfism
40.3.1 Clinical Appearance
40.3.1.1 Disproportionate Dwarfism
40.3.1.2 Proportionate Dwarfism
40.3.1.3 Others
40.3.2 Diagnosis
40.3.2.1 Disproportionate Dwarfism
40.3.2.2 Proportionate Dwarfism
40.3.2.3 Others
40.3.3 Correlation Between Phenotype and Genotype
40.3.3.1 Achondroplasia
40.3.3.2 Spondyloepiphyseal Dysplasia Congenita
40.3.3.3 Growth Hormone Deficiency
40.3.3.4 Others
40.3.4 Genetic Counseling
40.3.4.1 Achondroplasia
40.3.4.2 Spondyloepiphyseal Dysplasia Congenita
40.3.4.3 Combined Pituitary Hormone Deficiency
40.3.4.4 Others
40.3.5 Prenatal Diagnosis and Preimplantation Genetic Diagnosis
40.3.5.1 Achondroplasia
40.3.5.2 Others
40.3.6 Typical Clinical Case
40.4 Adrenopathy
40.4.1 Overview
40.4.1.1 Structure of Adrenal Gland
40.4.2 Cushing’s Syndrome
40.4.2.1 Pathogeny and Clinical Manifestation
40.4.2.2 Laboratory Diagnosis of Cushing’s Syndrome
40.4.2.3 Typical Medical Case
40.4.3 Primary Aldosteronism
40.4.3.1 Pathogeny and Clinical Appearance
40.4.3.2 Laboratory Diagnosis of Primary Aldosteronism
40.4.3.3 Genetic Testing
40.4.3.4 Typical Medical Case
40.4.4 Addison’s Disease
40.4.4.1 Epidemiology and Clinical Appearance
40.4.4.2 Laboratory Diagnosis of Addison’s Disease
40.4.4.3 Typical Medical Case
40.4.5 Pheochromocytoma
40.4.5.1 Overview
40.4.5.2 Laboratory Diagnosis of Pheochromocytoma
40.4.5.3 Genetic Testing
40.4.5.4 Typical Medical Case
40.4.6 Congenital Adrenocortical Hyperplasia
40.4.6.1 Overview
40.4.6.2 Laboratory Examination
40.4.6.3 Genetic Testing
40.4.6.4 Typical Medical Case
40.5 Gout
40.5.1 Overview
40.5.2 Clinical Appearance
40.5.3 Laboratory Diagnosis
40.5.3.1 Blood Uric Acid
40.5.3.2 Urine Uric Acid
40.5.3.3 Synovial Fluid Analysis
40.5.3.4 Other Blood Tests
40.5.3.5 Gene Testing
40.5.3.6 Others
40.5.4 Management
40.5.5 Conclusion
40.5.6 Typical Medical Case
References
41: Neurological Disease
41.1 Alzheimer’s Disease
41.1.1 Overview
41.1.2 Etiology
41.1.3 Clinical Appearance
41.1.4 Clinical Diagnosis
41.1.4.1 Diagnostic Criteria
41.1.4.2 Laboratory Diagnosis
Cerebrospinal Fluid (CSF) Biomarkers
Amyloid-β
Tau Protein
Blood-Based Biomarker Candidates
Aβ1–42:Aβ1–40 Ratio
Phosphorylated Tau Protein (P-Tau)
Neurofilament Light (NFL)
Classical Genetic Testing
Genes Implicated in EOAD
Genes Implicated in LOAD
Other Potential Genetic Risk Genes of AD
Candidate Epigenetics Biomarkers
DNA Methylation
Histone Modifications
MicroRNAs
Imaging Diagnosis
41.1.5 Management
41.1.6 Conclusion
41.1.7 Typical Medical Case
41.2 Glioma
41.2.1 Overview
41.2.2 Classification
41.2.2.1 By Type of Cell
41.2.2.2 By Grade
41.2.2.3 By Location
41.2.3 Signs and Symptoms
41.2.4 Causes and Pathogenesis
41.2.4.1 Genetic Factors
41.2.4.2 Adult Stature and Body Weight
41.2.4.3 Allergies and Other Medical Conditions
41.2.4.4 Dietary Factors
41.2.4.5 Ionizing Radiation
41.2.5 Molecular Markers in Gliomas
41.2.5.1 Loss of Heterozygosity (LOH) of 1p19q
41.2.5.2 IDH1 and IDH2 Mutations
41.2.5.3 MGMT Promotor Methylation
41.2.5.4 Germline Mutation of TP53
41.2.5.5 Important Factors in Glioma Biology
RTK/RAS/PI(3K), P53
IDH Mutation
Hypoxia, Pseudohypoxia, and Angiogenesis
41.2.6 Treatment
41.2.6.1 Surgical Resection
41.2.6.2 Radiation Therapy
41.2.6.3 Chemotherapy
41.2.7 Typical Medical Case
41.3 Muscular Dystrophy/Muscular Atrophy
41.3.1 Overview
41.3.2 Clinical Appearance
41.3.2.1 Muscular Dystrophy
Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD)
Congenital Muscular Dystrophy
Myotonic Dystrophy
Facioscapulohumeral Muscular Dystrophy
Limb-Girdle Muscular Dystrophy
Oculopharyngeal Muscular Dystrophy
Distal Myopathy
Emery-Dreifuss Muscular Dystrophy
41.3.2.2 Muscular Atrophy
Spinal Muscular Atrophy
Amyotrophic Lateral Sclerosis
41.3.3 Diagnosis
41.3.3.1 Muscular Dystrophy
DMD and BMD
CMD
DM
FSHD
LGMD
OPMD
Distal Myopathy
EDMD
41.3.3.2 Muscular Atrophy
SMA
ALS
41.3.4 Correlation between Phenotype and Genotype
41.3.4.1 Muscular Dystrophy
DMD/BMD
CMD
DM
FSHD
OPMD
Distal Myopathy
EDMD
41.3.4.2 Muscular Atrophy
SMA
ALS
41.3.5 Genetic Counseling
41.3.6 Prenatal Diagnosis and Preimplantation Genetic Diagnosis
41.3.7 Typical Clinical Case
41.4 Epilepsy
41.4.1 Overview
41.4.2 Diagnosis
41.4.3 Genetic Testing Algorithm
41.4.3.1 Exclude Nongenetic Disorders
41.4.3.2 Family History
41.4.3.3 General Physical and Neurologic Evaluations
41.4.3.4 Inherited Metabolic Disorders
41.4.4 Correlation between Phenotype and Genotype
41.4.5 Genetic Counseling
41.4.6 Prenatal Diagnosis and Preimplantation Genetic Diagnosis
41.4.7 Typical Clinical Case
References
42: Reproductive Organ Cancer
42.1 Breast Cancer
42.1.1 Overview
42.1.2 Anatomy of the Breast
42.1.3 Histological Classification
42.1.4 Surveillance and Diagnosis
42.1.4.1 Imaging Technologies and Applications in Early Diagnosis and Prognosis for Breast Cancer
42.1.4.2 Mammography
42.1.4.3 Ultrasound
42.1.4.4 Magnetic Resonance Imaging
42.1.4.5 Breast Cancer Biomarkers for Risk Assessment, Screening, Detection, Diagnosis, and Prognosis
42.1.4.6 Genomic Biomarkers
42.1.4.7 Epigenomic Biomarkers and Methylation Biomarkers
42.1.4.8 miR Biomarkers
42.1.4.9 Breast Circulating Tumor Cells Potential Biomarkers for Breast Cancer Diagnosis and Prognosis Evaluation
42.1.4.10 Tumor-Specific Protein 70 (SP70)
42.1.4.11 Other Protein Markers
42.1.5 Typical Medical Case
42.2 Ovarian Cancer
42.2.1 Overview
42.2.2 Clinical Appearance
42.2.3 Laboratory Diagnosis
42.2.3.1 Tumor Markers
CA125
Human Epididymis 4 (HE4)
Mesothelin
Osteopontin
Kallikreins
B7-H4
Interleukins
Vascular Endothelial Growth Factor (VEGF)
MicroRNAs
Exosomes
Circulating Cell-Free DNA
42.2.3.2 Genetic Test
Genetic Mutation
Epigenetic Regulation
42.2.4 Management
42.2.5 Conclusion
42.2.6 Typical Medical Case
42.3 Cervical Cancer
42.3.1 Overview
42.3.1.1 Staging and Classification
42.3.1.2 HPV Introduction
HPV Infection Procedure in the Cervix
Ingestion of the Virus and Delivery of the Genome to Nucleus
Virus Transcription and Life Cycle
Self-limiting and Persistent Infection of the Virus
42.3.2 Clinical Appearance
42.3.3 Laboratory Diagnosis
42.3.3.1 Papanicolaou Test (Pap Test)
42.3.3.2 Molecular Marker
Squamous Cell Carcinoma Antigen (SCCA)
Serum Fragments of Cytokeratin (CYFRA)
42.3.4 Management
42.3.5 Conclusion
42.3.6 Typical Medical Case
References
43: Prenatal Diagnosis and Preimplantation Genetic Diagnosis
43.1 Noninvasive Prenatal Testing
43.1.1 Overview
43.1.2 Laboratory Examination
43.1.2.1 Cell-Free Fetus DNA(cffDNA) and Its Detection in Maternal Plasma
43.1.2.2 Fetal Nucleated Red Blood Cells
43.1.3 Clinical Application
43.1.3.1 Chromosomal Aneuploidy
43.1.3.2 Subchromosomal Abnormalities
43.1.3.3 Single Gene Mutations
43.1.3.4 Fetal Sex Determination
43.1.3.5 Hemolytic Disease of the Newborn
43.1.3.6 Other Applications
43.1.4 Summary
43.1.5 Typical Medical Case
43.2 Mitochondrial Deafness
43.2.1 Introduction
43.2.1.1 Mitochondria and Mitochondrial Genome
43.2.1.2 Mitochondrial Diseases
43.2.1.3 Deafness and Mitochondrial Deafness
43.2.2 Clinical Appearance
43.2.2.1 Mitochondrial Syndromic Hearing Loss
Kearn-Sayre Syndrome
Mitochondrial Encephalopathy with Lactic Acidosis, and Stroke-like episodes
Myoclonic Epilepsy with Ragged Red Fibers
43.2.2.2 Mitochondrial Non-Syndromic Hearing Loss
MT-RNR1 Related Mitochondrial Hearing Loss
Sensorineural Hearing Impairment Induced by Aminoglycosides
Sensorineural hearing impairment without aminoglycosides exposure
MT-TS1 Related Mitochondrial Hearing Loss
43.2.3 Diagnosis
43.2.3.1 Mitochondrial Sensorineural Hearing Loss
Initial Diagnosis
Establishing the Diagnosis
43.2.3.2 Differential Diagnosis
Aminoglycosides-Induced Ototoxicity
43.2.4 Management
43.2.4.1 Treatment of Manifestations
43.2.4.2 Prevention of Primary Manifestations
43.2.4.3 Prevention of Secondary Complications
43.2.4.4 Surveillance
43.2.4.5 Agents and Circumstances to Avoid
43.2.4.6 Evaluation of Relatives at Risk
43.2.5 Prenatal Diagnosis and Preimplantation Genetic Diagnosis in Mitochondrial Deafness
43.2.5.1 Prenatal Diagnosis in Mitochondrial Deafness
43.2.5.2 Preimplantation Genetic Diagnosis in Mitochondrial Deafness
43.2.6 Conclusion
43.2.7 Internet Resources
43.3 Hereditary Vascular Retinopathy
43.3.1 Overview
43.3.1.1 The Anatomy of the Retina
43.3.1.2 The Physiology of the Retinal Vessels
43.3.1.3 The Examination of the Retina
43.3.2 von Hippel-Lindau Syndrome
43.3.2.1 Overview
43.3.2.2 Clinical Appearance
43.3.2.3 Examination
43.3.2.4 Diagnosis
43.3.2.5 Genotype–Phenotype Correlations
43.3.2.6 Differential Diagnosis
Isolated Hemangioblastoma or RCC
Pheochromocytoma
RCC
43.3.2.7 Management
43.3.2.8 Genetic Counseling
43.3.3 Retinal Vasculopathy with Cerebral Leukodystrophy
43.3.3.1 Overview
43.3.3.2 Clinical Appearance
43.3.3.3 Examination
43.3.3.4 Diagnosis
43.3.3.5 Genotype–Phenotype Correlations
43.3.3.6 Differential Diagnosis
43.3.3.7 Management
43.3.3.8 Genetic Counseling
43.3.4 Familial Exudative Vitreoretinopathy
43.3.4.1 Overview
43.3.4.2 Clinical Appearance
43.3.4.3 Examination
43.3.4.4 Diagnosis
43.3.4.5 Genotype–Phenotype Correlations
43.3.4.6 Differential Diagnosis
Retinopathy of Prematurity
Coats Disease
Persistent Hyperplastic Primary Vitreous
Norrie Disease
Toxocariasis
43.3.4.7 Management
43.3.4.8 Genetic Counseling
43.3.5 Typical Medical Case
References
44: Transplant Matching
44.1 Overview
44.1.1 Hyperacute Rejection
44.1.2 Acute Rejection
44.1.3 Chronic Rejection
44.2 HLA and Transplantation Matching
44.2.1 Overview
44.2.2 Genetic Characteristics of HLA
44.2.2.1 Phenotype, Monotype, and Genotype
44.2.2.2 HLA Genetic Model
Monotype Inheritance
Codominant Inheritance
Linkage Disequilibrium
44.3 Tissue Matching Technology and Related Experiments
44.3.1 HLA Typing
44.3.1.1 HLA Serological Typing Technology
44.3.1.2 HLA Genotyping Technology
44.3.1.3 The Basis of HLA Genotyping–Polymerase Chain Reaction
44.3.1.4 Restriction Fragment Length Polymorphism Typing
44.3.1.5 Single Strand Conformation Polymorphism Typing
44.3.1.6 Sequence-Specific Primers Typing
44.3.1.7 PCR-Sequence Specific Oligonucleotide Probe Hybridization
The Basic Principle of PCR-SSO
PCR-SSO Reverse Hybridization Typing
Flow Cytometry-SSO Typing Method
44.3.1.8 Gene Chip Typing
Basic Principle
Advantages of Gene Chip
44.3.1.9 HLA Typing Based on Sequence-Based Typing
44.3.2 HLA Antibody Detection
44.3.2.1 Complement Dependent Cytotoxicity
44.3.2.2 ELISA
44.3.2.3 Flow Fluorescent Microsphere Method
44.3.3 MICA Antibody Analysis
44.3.4 Non-HLA Antibodies
44.3.5 Cross-Matching Experiment of Donor and Recipient
44.3.6 Monitoring of Drug Concentration After Transplantation
44.3.7 Detection of Pathogens Associated with Infection After Transplantation
44.3.8 Routine Blood Cell Analysis and Biochemical Index Detection
44.4 Clinical Significance of HLA Matching in Organ Transplantation
44.4.1 HLA and Kidney Transplantation
44.4.2 HLA and Liver Transplantation
44.4.3 HLA and Heart Transplantation
44.4.4 HLA and Lung Transplantation
References
45: Paternity Testing
45.1 Overview
45.1.1 Alleged Father (AF) /Alleged Mother (AM)
45.1.2 Genetic Marker
45.1.3 Genetic Law
45.1.4 Basic Principles of Paternity Testing
45.2 Several Common Paternity Testing Techniques
45.2.1 Paternity Exclusion by Red Blood Cell Type
45.2.2 Paternity and Family Relationship Identification by DNA Fingerprint Techniques
45.3 Judgement and Analysis of Paternity Testing Results
45.3.1 Parent-Child Relationship Exclusion
45.3.1.1 Excluding Probability of Paternity (EP)
45.3.1.2 Calculation of Excluding Probability of Paternity (EP)
45.3.1.3 Cumulative Excluding Probability of Paternity (CEP)
45.3.1.4 Errors in Excluding Parent-Child Relationship and Its Solutions
45.3.2 Affirmation of Parent-Child Relationship
45.3.2.1 Paternity Index
45.3.2.2 Relative Chance of Paternity
45.3.3 Forensic Criteria of Paternity Testing
45.3.3.1 The Standard of Paternity Exclusion
45.3.3.2 The Standard of Paternity Affirmation
45.3.4 Laboratory Standards of Paternity Testing
45.4 Collection and Preservation of Paternity Test Samples
45.4.1 Collection of Paternity Test Samples
45.4.1.1 Blood/Bloodstain
45.4.1.2 Hair
45.4.1.3 Oral Swab
45.4.1.4 Saliva and Saliva Spots
45.4.1.5 Amniotic Fluid Samples
45.4.2 Preservation of Paternity Test Samples
References
Appendixes
Appendix A: Tests of Infectious Disease
Appendix B: Cancer Tests
Appendix C: Tests of Genetic Disease
Appendix D: Pharmacogenomics
D.1 Anticoagulation Therapy
D.2 Antihypertensive Therapy
D.3 Anticardiac Insufficiency
D.4 Antiangina Pectoris Treatment
D.5 Anti-inflammatory Treatment
D.6 Antigout Treatment
D.7 Antipeptic Ulcer Treatment
D.8 Antidepressant Therapy
D.9 Antipsychotic Treatment
D.10 Antiepileptic Treatment
D.11Antileukemia Treatment
D.12 Antineoplaston
D.13 Antifungal Therapy
D.14 Anti-hyperthyroidism
D.15 Anti-tuberculosis Treatment
D.16 Antiasthma treatment
D.17 Anesthetic Treatment of Paroxysmal Pain
D.18 Disease Prevention
D.19 Erectile Dysfunction
D.20 Hypoglycemic Therapy
D.21 Immunosuppressive Therapy
D.22 Lipid Control Therapy
D.23 Risk Profile