Genetic disorders have been the focus of scientists for a long time. The emergence of next-generation sequencing techniques has ushered a new era in genetics and several developments have occurred in human genetics. The scientific perspective has also been widened with omics technologies that allow researchers to analyze genetic sequences and their expression products. An integrated approach is being used not only for diagnosis but also for disease management and therapeutic purposes.
This book highlights emerging areas of omics technology and its application in the diagnosis and management of human genetic disorders. The book covers three areas of research and implementation:
1) Diagnosis (covering conventional strategies to next-generation platforms). This section focuses on the role of in silico analysis, databases and multi-omics of single-cell which will help in designing better
management strategies.
2) Disease Management and therapeutic interventions. This section starts with genetic counselling and progresses to more specific techniques such as pharmacogenomics and personalized medicine, gene editing techniques and their applications in gene therapies and regenerative medicine.
3) Case studies. This section discusses the applications and success of all the above-mentioned strategies on selected human disorders.
This book serves as a handy reference for students and academics studying advanced omics techniques in biochemistry and molecular genetics as part of courses in life sciences, pharmacology and medicine.
Author(s): Syeda Marriam Bakhtiar, Erum Dilshad
Publisher: Bentham Science Publishers
Year: 2022
Language: English
Pages: 333
City: Singapore
Cover
Title
Copyright
End User License Agreement
Contents
Foreword
Preface
List of Contributors
Next-Generation Technologies for Rare Inherited Disorders
Hira Kazmi1 and Muhammad Ilyas2,3,*
1. INTRODUCTION
1.1. Whole Genome/Exome Sequencing
1.2. Transcriptomics (RNA-Seq) of Rare Diseases
1.3. DNA Methylation (Methyl-Seq) in Rare Diseases
1.4. Long-Reads Sequencing for Rare Inherited Disorders
1.5. The International Rare Diseases Research Consortium
CONCLUSION AND RECOMMENDATIONS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Genetic Testing for Rare Genetic Disorders
Muhammad Tariq1,*, Naveed Altaf Malik1, Ilyas Ahmad2, Syeda Seema Waseem and Shahid Mahmood Baig1
1. INTRODUCTION
1.1. Genetic Testing and Its Scope
1.2. Screening and Diagnostic Testing
1.3. Why Genetic Testing?
2. TESTING TECHNOLOGIES
2.1. Detection of Targeted Allele Specific Mutation
2.2. Gene-specific Sanger Sequencing
2.3. Testing for Structural Variations
2.4. Genetic Testing in the NGS Era
3. INCIDENTAL FINDINGS
4. FUTURE PROSPECTS AND CHALLENGES
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Preimplantation, Prenatal, and Postnatal Diagnosis
Sadia Nawaz1,* and Humna Masood1
1. INTRODUCTION
1.1. Preimplantation Genetic Diagnosis (PGD)
1.1.1. PGD and In vitro Diagnostic Procedures
1.1.2. Phases of PGD
1.1.3. Embryo Biopsy
1.1.4. Genetic Diagnostic Analysis
1.2. Prenatal Diagnosis (PND)
1.2.1. In Vivo Procedure of PND
1.2.2. Sampling of Fetus Cells
1.2.3. Genetic Diagnostic Analysis
1.3. Postnatal Diagnosis
1.3.1. Chromosomal Abnormalities
1.3.2. Monogenic (Mendelian) Diseases
1.3.3. Polygenic Diseases
2. PREIMPLANTATION, PRENATAL, AND POSTNATAL DIAGNOSTIC TECHNIQUES
2.1. Array Comparative Genomic Hybridization (aCGH)
2.2. Fluorescence In Situ Hybridization (FISH)
2.3. Next Generation Sequencing (NGS)
2.4. Whole Genome Amplification (WGA)
3. PRENATAL AND POSTNATAL DIAGNOSTIC TECHNIQUES FOR CHROMOSOMAL ABNORMALITIES, MONOGENIC, AND POLYGENIC DISEASES
3.1. Methylation PCR
3.2. Amniocentesis
3.3. Karyotyping
3.4. Multiplex Ligation Dependent Probe Amplification (MLPA)
3.5. Restriction Fragment Length Polymorphism (RFLP)
3.6. Quantitative Fluorescence Polymerase Chain Reaction (QF-PCR)
3.7. Cell Free Fetal DNA Analysis
3.8. Chromosomal Microarray Analysis
3.9. Chorionic Villus Sampling
4. FUTURE CHALLENGES IN PREIMPLANTATION, PRENATAL AND POSTNATAL DIAGNOSIS
5. FUTURE PROSPECTS
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Genetic Counseling in Inherited Disorders
Shumaila Zulfiqar1,2, Muhammad Tariq1,*, Naveed Altaf Malik1, Ayaz Khan1, Shafaq Ramzan1, Maria Iqbal1,3, Iram Anjum2 and Shahid Mahmood Baig1
1. INTRODUCTION
2. POPULATION CARRIER SCREENING MECHANISM
2.1. Thalassemia a Case Study
3. RISK ESTIMATION
4. CLINICAL PRACTICES
5. ETHICAL ISSUES
6. FUTURE PROSPECTS
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Genome-Wide Association Studies (GWAS)
Hafiza Noor Ul Ayan1,2 and Muhammad Tariq1,*
1. INTRODUCTION
1.1. Rationale
2. BENEFITS OF GWAS
3. SUCCESS STORIES
3.1. Type 2 Diabetes
3.2. Autoimmune Diseases
3.3. Coronary Artery Disease (CAD)
4. LIMITATIONS OF GWAS
5. POST-GWAS ERA: PROSPECTS AND CHALLENGES
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Regenerative Medicine
Hajra Qayyum1,* and Syeda Marriam Bakhtiar1
1. INTRODUCTION
2. APPROACHES TO RM
2.1. Cell-based Therapy
2.1.1. Adult Stem Cells
2.1.2. Pluripotent Stem Cell-Based Cell Therapies
2.2. Biomaterials
2.3. Implantation of Scaffold Seeded with Cells
3. CLINICAL APPLICATIONS (CASE STUDIES)
3.1. Bladder and Urethra
3.2. Blood Vessels
3.3. Heart
3.4. Liver
3.5. Skin
3.6. Bone
3.7. Cartilage Tissue
4. CHALLENGES AND FUTURE PERSPECTIVES
4.1. Lack of Robust Lineage-Specific Differentiation Protocols
4.2. Tumorigenicity
4.3. Immune Rejection
4.4. Heterogeneity
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Emerging OMICS and Genetic Disease
Muhammad Jawad Hassan1,*, Muhammad Faheem1 and Sabba Mehmood1
1. INTRODUCTION TO OMICS AND GENETIC DISEASE
2. ADVANCED TECHNIQUES IN “OMICS”
2.1. Emerging Omics Techniques: Genomics and Transcriptomics
2.1.1. Genomics
2.1.2. Transcriptomics
2.2. Emerging Omics Techniques: Proteomics and Metabolomics
2.2.1. Proteomics
2.2.2. Metabolomics
3. OMICS AND DIAGNOSIS OF GENETIC DISEASES
3.1. Back To The Future
3.2. Advances In Omics Technologies For Disease Diagnosis (examples)
3.3. Mendelian Disorders
3.4. Non-mendelian/common Disorders
4. OMICS DATABASES
5. OMICS: GENETIC DISEASE MANAGEMENT AND THERAPEUTICS
6. CHALLENGES AND OPPORTUNITIES
6.1. Reference Populations and Phenotyping
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Integrated Bioinformatics and Computational Biology Approaches: Applications in Diagnosis and Therapeutics
Fatima Shahid1, Shifa Tariq Ashraf1, Hayeqa Shahwar Awan1, Amina Basheer1 and Amjad Ali1,*
1. INTRODUCTION
1.1. Exploration of Disease-Associated Biomarkers
1.2. Computational Models as Tools to Identify Key Biomarkers
1.3. Annotation of Disease Associated Mutations
1.4. Identification of Epigenetic Drivers
2. ROLE OF SYSTEMS BIOINFORMATICS (NETWORK-BASED METHODS FOR HUMAN DISEASE GENE PREDICTION)
2.1. Systems Modelling and Simulation
2.2. Network-Based Diagnostics and Therapeutics
2.3. Tools/ Data Bases Used in Diagnosis and Treatment Regimens
2.4. Contribution of Bioinformatics in Cancer Diagnostics and Therapeutics
3. APPLICATION IN PRECISION MEDICINE AND PHARMACOGENOMICS
3.1. Pharmacogenomics and Pharmacogenetics in Personalized Medicine
3.2. Pharmacogenomics and Pharmacogenetics in Drug Development
3.3. Pharmacogenomics in Establishment of Drug Application Guidelines
4. REVERSE VACCINOLOGY-A PROGRESSIVE STEP TOWARDS THERAPEUTIC INNOVATION
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Multi-omics Data Integration: Applications in Systems Genomics
Anam Naz1,*, Ammara Siddique2, Aqsa Ikram1, Bisma Rauff5, Huma Tariq3 and Sajjad Ahmed4
1. INTRODUCTION
1.1. Advanced Techniques in “Omics”
1.2. Omics-Driven Targeted Therapy
1.3. Meta-omics
1.4. Transcriptomics
1.5. Single-Dimensional Transcriptomic Assessment versus Integrated Omics
1.6. Rewards of Integrated Omics
2. PATHWAY PROFILING USING SYSTEM GENOMICS
3. CATEGORIES OF PATHWAY PROFILING AND GENETIC NETWORK
3.1. Metabolic Pathway Profiling
3.2. Signaling Pathways Profiling
3.3. Networks for Protein-Protein Interaction
3.4. Gene Regulatory Networks
4. DESIGNING EXPERIMENTS FOR OMICS DATA INTEGRATION
4.1. Multi-Omics Data from Genome to Phenome: Integration in Systems Genomics
4.2. Software and Tools Used for Integration
4.3. Multi-Omics Factor Analysis (MOFA)
4.4. MixOmics
4.5. Graph-based Clustering of Samples
4.6. Nonnegative Matrix Factorization (NMF)
4.7. Multi-Omics Data Integration (miodin)
4.8. Network-based Integration of Multi-omics Data (NetICS)
4.9. moCluster
4.10. Penalized Multivariate Analysis (PMA)
5. CHALLENGES
6. FUTURE ASPECTS
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Single Cell Omics
Erum Dilshad1,*, Amna Naheed Khan1, Iqra Bashir1, Muhammad Maaz1, Maria Shabbir2 and Marriam Bakhtiar1
1. INTRODUCTION
1.1. Single-cell genomics
Single-cell transcriptomics
1.3. Single-cell Proteomics
1.4. Single-cell Metabolomics
2. STRATEGIES FOR SINGLE-CELL ISOLATION
2.1. Fluorescence-Activated Cell Sorting (FACS)
2.2. Magnetic-activated Cell Sorting (MACS)
2.3. Laser Capture Micro-dissection (LCM)
2.4. Manual Cell Picking/micro-manipulation
2.5. Micro-fluidics
3. STRATEGIES FOR SINGLE-CELL SEQUENCING
3.1. Multiple Displacement Amplification
3.2. Multiple Annealing And Looping Based Amplification Cycles
3.3. PCR Based scRNA Sequencing
3.4. In vitro Transcription (IVT)-based Amplification
3.5. Mass Spectrometry
3.6. Single-cell multi-Omics
3.7. Multi-Omics Approaches: Challenges and Opportunities
4. STRATEGIES FOR MULTI-OMICS PROFILING OF SINGLE CELLS
4.1. Combined
4.2. Separate
4.3. Split
4.4. Convert
4.5. Predict
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Pharmacogenomics
Shumaila Azam1, Sahar Fazal1,*, Attiya Kanwal2, Muhammad Saad Khan5, Narjis Khatoon1, Muneeba Ishtiaq1, RabbiahManzoor Malik1, 3, Sana Elahi1 and Fakhra Nazir1, 4
1. INTRODUCTION
1.1. Application of Pharmacogenomics
1.2. Translating Pharmacogenomics
1.3. Challenges in Pharmacogenomics
1.4. Design and Interpretation of Pharmacogenetics and Pharmacogenomics Studies
1.5. Regulatory Issues in Genetic Testing
1.6. Development of New Genomic Technologies
1.7. Ethical Issues
1.8. Education
1.9. Cost
2. ANTICIPATED BENEFITS OF PHARMACOGENOMICS
2.1. More Powerful Medicines
2.2. Better, Safer Drugs the First Time
2.3. More Accurate Methods of Determining Appropriate Drug Dosages
2.4. Advanced Screening for Disease
2.5. Better Vaccines
2.6. Improvements in the Drug Discovery and Approval Process
2.7. Decrease in the Overall Cost of Health Care
3. PHARMACOGENOMICS TODAY
4. FUTURE OF PHARMACOGENOMICS
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Biomaterials in Gene Therapy for Soft and Hard Tissues
Sarmad Mehmood1, Sajjad Haider2, Muhammad Naeem3, Raees Khan4, Muhammad Faheem3, Bushra Bano4, Syeda Marriam Bakhtiar5, Atif Ali Khan Khalil3, Fazli Subhan3, Syed Babar Jamal3,* and Adnan Haider3,*
1. INTRODUCTION
2. MECHANISM OF GENE THERAPY
2.1. Delivery of Gene for Gene Therapy
2.1.1. Gene Release
2.1.2. Hematopoietic Stem Cells and Gene Therapy
2.1.3. Gene Therapy via T Cells of a Chimeric Antigen (CAR-T)
2.1.4. CRISPR-Cas9
2.1.5. Ethical Issues
3. TYPES OF GENE DELIVERY CARRIERS
3.1. Viral Vectors
3.1.1. Polymeric Vectors
3.1.2. Natural Polymeric Vectors
3.1.3. Synthetic Polymeric Vectors
3.2. Non-Viral Vectors
4. BIOMATERIALS FOR GENE THERAPY
5. GENE THERAPY IS SOFT AND HARD TISSUE (EXAMPLES)
5.1. Muscle Tissue
5.2. Nerve Tissue
5.3. Bone Tissues
5.4. Non-Viral Gene Therapy for Bone Engineering
6. FUTURE PROSPECTS
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Induced Pluripotent Stem Cells
Ambrin Fatima1,*, Uzma Abdullah2 and Zafar Ali3
1. HUMAN EMBRYONIC STEM CELLS
1.1. Human Induced Pluripotent Stem Cells: Origins and Properties
1.2. Applications of Induced Pluripotent Stem Cells
1.3. Disease modelling
1.4. Embryoid Bodies: An in vitro Model of Embryogenesis
1.5. 2D Models
1.6. 3D Models (Examples)
1.7. Drug Testing and Personalized Medicine
1.8. Stem Cell Therapy and Regenerative Medicine
1.9. CHALLENGES TO IPSC-BASED DISEASE MODELLING AND DRUG DISCOVERY/CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Hemoglobinopathies
Mahnoor Asif1, Sadia Nawaz2,* and Muhammad Tariq1
1. INTRODUCTION
1.1. Structure and Genetics of Hemoglobin Synthesis
1.2. α-, β-, γ- and δ-Thalassemia and Related Conditions
1.3. Sickle Cell Hemoglobin
1.4. Other Hemoglobinopathies
2. MOLECULAR DIAGNOSIS OF HEMOGLOBINOPATHIES
2.1. Hemoglobinopathy Screening in Pregnancy
2.2. Diagnosis of Hemoglobinopathies: New Scientific Advances
2.3. Recent Advances in Screening and Diagnosis of Hemoglobinopathies
2.4. New Challenges in the Diagnosis of Hemoglobinopathies: Migration of Populations
3. BLOOD TRANSFUSION THERAPY IN HEMOGLOBINOPATHIES
4. CRISPR-CAS9 GENE EDITING FOR HEMOGLOBINOPATHIES
5. CHALLENGES
6. FUTURE PROSPECTS
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Metabolic Syndromes
Mahnoor Ejaz1,*, Areena Suhail Khan2, Faiza Naseer3 and Alvina Gul1
1. INTRODUCTION
1.1. Background
1.2. Components of MetS
1.2.1. Obesity
1.2.2. Type2 Diabetes
1.2.3. Atherosclerotic Cardiovascular Disease (ASCVD)
1.3. Diagnostic Criteria For Metabolic Syndrome
1.3.1. Clinical Measures For Diagnosis
1.3.2. Elevated Waist Circumference
1.3.3. Elevated Triglycerides
1.3.4. Low HDL-C
1.3.5. Elevated Blood Pressure
1.3.6. Elevated Fasting Glucose
1.3.7. Others (Pro-inflammatory State)
1.3.8. Genetic Determinants of MetS
2. THERAPEUTICS OF METABOLIC DISORDERS
2.1. Pharmacological Therapy
2.1.1. Polypill-Addresses More Than One Cardiometabolic Risk
2.2. Fixed Dose Combination (FDC)
2.2.1. Diabetes
2.2.2. SGLT 2 Inhibitor/DPP 4 Inhibitor
2.2.3. Thiazolidinedione/DPP-4 Inhibitor
2.2.4. Biguanide/DPP-4 Inhibitor FDC
2.2.5. Biguanide/α-Glucosidase Inhibitor
2.2.6. Insulin Combinations
2.2. Diabesity
2.3. Hyperthyroidism
2.4. Methimazole/Triiodothyronine
3. SURGICAL TREATMENT
3.1. Bariatric Treatment
3.1.1. Diabesity
3.1.2. Dyslipidemia
4. GENE THERAPY
4.1. Leptin Gene Therapy
4.1.1. Diabetes
4.1.2. Diabesity
4.2. ZFN Gene Editing
4.3. CRISPR/ Cas9 Genome Editing
5. GOAL OF THERAPY
CONCLUDING REMARKS
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Intellectual Disabilities
Zafar Ali1,*, Uzma Abdullah2 and Ambrin Fatima3
1. INTRODUCTION
2. DIAGNOSIS AND CLASSIFICATION OF ID
3. AUTISM SPECTRUM DISORDERS (ASD)
4. MICROCEPHALY
5. ETIOLOGY OF INTELLECTUAL DISABILITIES
6. GENETIC FACTORS
7. DIAGNOSIS
8. TREATMENT
9. PSYCHOTROPIC DRUG INTERVENTIONS
10. SPECIAL EDUCATION
11. INTERVENTION FOR INBORN ERRORS OF METABOLISM
11.1. GENE THERAPY
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Primary Microcephaly and Schizophrenia: Genetics, Diagnostics and Current Therapeutics
Iram Anjum1,*, Aysha Saeed1, Komal Aslam1,2, Bibi Nazia Murtaza3 and Shahid Mahmood Baig4
1. INTRODUCTION
2. PRIMARY MICROCEPHALY
2.1. Clinical Attributes
2.2. Types of Microcephaly
2.3. Incidence
2.4. Genetics of Primary Microcephaly
2.5. Diagnosis
2.6. Management
3. SCHIZOPHRENIA
3.1. Clinical Attributes
3.2. Types of Schizophrenia
3.2.1. Paranoid Schizophrenia
3.2.2. Disorganized Schizophrenia
3.2.3. Catatonic Schizophrenia
3.2.4. Undifferentiated Schizophrenia
3.2.5. Residual Schizophrenia
3.3. Incidence
3.4. Genetics of Schizophrenia
3.5. Diagnosis
3.6. Management
CONCLUSION
CONSENT FOR PUBLICATION
CONFLICT OF INTEREST
ACKNOWLEDGEMENTS
REFERENCES
Subject Index
