The Genetics of Neurodevelopmental Disorders.

Intro -- Table of Contents -- Foreword -- Chapter 1: The Genetic Architecture of Neurodevelopmental Disorders -- 1.1 Introduction -- 1.2 Theoretical Considerations -- 1.3 Empirical Evidence -- 1.4 Complex Genotype-Phenotype Relationships -- References -- Chapter 2: Overlapping Etiology of Neurodevelopmental Disorders -- 2.1 Introduction -- 2.2 A Brief History of Neurodevelopmental Disorders -- 2.3 Evidence of Comorbidity in Individual Patients -- 2.4 Familial Co-Occurrence of NDD -- 2.5 Environmental Risk Factors in Neurodevelopmental Disorders -- 2.6 Genomics Studies of NDD -- References -- Chapter 3: The Mutational Spectrum of Neurodevelopmental Disorders -- 3.1 Introduction -- 3.2 Rare CNV Contribute to Risk of Neurodevelopmental Disorders -- 3.3 Rare Coding Variants in Single Genes that Cause Neurodevelopmental Disorders -- 3.4 The Rate of Human Mutation, Paternal-Age Affect and Evolution -- 3.5 The Rare Versus Common Variant Debate for Neurodevelopmental Disorders -- 3.6 The Emerging Portrait -- References -- Chapter 4: The Role of Genetic Interactions in Neurodevelopmental Disorders -- 4.1 Introduction -- 4.2 Why Should Epistasis be Common? -- 4.3 Detecting Epistasis in Genetic Association Studies -- 4.4 Epistasis Case Studies for Neurodevelopmental Disorders -- References -- Chapter 5: Developmental Instability, Mutation Load, and Neurodevelopmental Disorders -- 5.1 Developmental Instability Theory -- 5.2 Evidence that Mutations Matter: Indirect Markers -- 5.3 Evolutionary Perspectives on Mutations -- 5.4 Evidence That Mutations Matter -- 5.5 General Mechanisms -- References -- Chapter 6: Environmental Factors and Gene-Environment Interactions -- 6.1 Introduction -- 6.2 How to Build a Brain -- 6.3 Cautionary Note on the Interpretation of Risk Factors -- 6.4 Risk Factors Associated with Neurodevelopmental Disorders.

6.5 Epidemiological Frameworks Can Improve Sampling for Genetic Studies -- 6.6 Combing Clues from Genetics and Epidemiology -- 6.7 Linking Genetics and the Environment - Specific Candidate Studies -- 6.8 Linking Genetics and the Environment - Genome-Wide Approaches -- 6.9 Summary and Conclusions -- References -- Chapter 7: The Genetics of Brain Malformations -- 7.1 Introduction -- 7.2 The Microcephalies -- 7.3 The Lissencephalies -- 7.4 The Polymicrogyrias -- 7.5 Brain Overgrowth and Somatic Mutations in the AKT/TOR Pathway -- 7.6 The Ciliopathies: Signaling at the Primary Cilium and Brain Development -- 7.7 Implications for Neuropsychiatric Disorders -- 7.8 Where Do We Go from Here? -- References -- Chapter 8: Disorders of Axon Guidance -- 8.1 Introduction -- 8.2 Axon Guidance Molecules -- 8.3 Axon Guidance Defects of Oculomotor Nerves -- 8.4 Contribution of Axon Guidance Genes to Neuropsychiatric Disorders -- 8.5 Conclusion/perspectives -- References -- Chapter 9: Synaptic Disorders -- 9.1 Introduction -- 9.2 Processes of Synapse Formation and Plasticity -- 9.3 Rare Syndromes -- 9.4 Enrichment for Synaptic Genes in Pathogenic Copy Number Variants -- 9.5 Whole-Exome Sequencing and Pathway Analyses in ASD, Schizophrenia, and ID -- 9.6 Functional Classes of Genes Implicated in Synaptic Disorders -- 9.7 Overview of Clinical Genetics Findings -- 9.8 Pathogenic Mechanisms -- 9.9 Cellular and Animal Models and the Development of New Therapies -- References -- Chapter 10: Human Stem Cell Models of Neurodevelopmental Disorders -- 10.1 Introduction -- 10.2 Modeling Human Brain Development and Disease in Rodents -- 10.3 Pluripotent Stem Cells -- 10.4 Directed Differentiation of Human Pluripotent Stem Cells to Replay Neural Development -- 10.5 Direct Differentiation and Transdifferentiation -- 10.6 Generation of Cerebral Cortex Neural Circuitry.

10.7 3D Models of Brain Development -- 10.8 PSC Models of Neurodevelopmental Disorders -- 10.9 Future Directions -- References -- Chapter 11: Animal Models for Neurodevelopmental Disorders -- 11.1 Animal Models - What are They Good For? -- 11.2 Defining Validity -- 11.3 If You Had to Choose Just One… -- 11.4 Understanding Penetrance and Variable Expressivity -- 11.5 What Should We Expect to Observe? -- 11.6 A Proposed Four-Tiered Analysis of Animal Models for Neurodevelopmental Disorders -- 11.7 An Added Dimension -- 11.8 Convergent Findings? -- 11.9 Generating a Genetically Modified Animal Model - Targeting a Gene or Locus -- 11.10 Targeting Strategies -- 11.11 Paying Attention to Genotype -- 11.12 Strain Effects and Modifier Loci -- 11.13 Rodents Aren't Everything -- 11.14 Neurobiologically-Driven Therapeutics in Neurodevelopmental Disorders -- 11.15 Conclusions -- References -- Chapter 12: Cascading Genetic and Environmental Effects on Development: Implications for Intervention -- 12.1 Introduction -- 12.2 Neurodevelopmental Disorders of Known Versus Unknown Genetic Origin -- 12.3 Environmental Influences -- 12.4 Phenotypes Are Emergent -- 12.5 Implications for Intervention -- 12.6 Learning Theories Driving Behavioral Interventions -- 12.7 Concluding Thoughts -- References -- Chapter 13: Human Genetics and Clinical Aspects of Neurodevelopmental Disorders -- 13.1 Introduction -- 13.2 Clinical classifications and the genetic architecture of disease -- 13.3 De novo mutations, germline mosaicism, and other complexities -- 13.4 Rare and compensatory mutations -- 13.5 Current ability/approaches -- 13.6 Prenatal diagnosis, preimplantation genetic diagnosis/screening -- 13.7 Implications for acceptance, prognosis and treatment -- 13.8 Conclusions -- 13.9 Acknowledgements -- References.

Chapter 14: Progress Toward Therapies and Interventions for Neurodevelopmental Disorders -- 14.1 Introduction -- 14.2 Genetics -- 14.3 Molecular Pathways as Targets for Therapeutic Intervention -- 14.4 Strategies for Intervention -- 14.5 Finding the Right Model -- 14.6 Animal Models for Neurodevelopmental Disorders -- 14.7 The Promise of Induced Pluripotent Stem Cells for Personalized Medicine -- 14.8 Neurotechnologies for Neurodevelopmental Disorders -- 14.9 Biological Markers and Clinical Markers -- 14.10 Conclusions -- References -- Subject Index -- Gene Index -- End User License Agreement.

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Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, 2024. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries.