Rosenberg's molecular and genetic basis of neurological and psychiatric disease. Volume 1 /

Rosenberg's Molecular and Genetic Basis of Neurologic and Psychiatric Disease, Seventh Edition, provides a comprehensive introduction and reference to the foundations and key practical aspects relevant to neurologic and psychiatric disease. This volume has been thoroughly revised and includes n...

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Bibliographic Details
Corporate Author: ScienceDirect (Online service)
Other Authors: Rosenberg, Roger N. (Editor), Pascual, Juan M. (Editor)
Format: eBook
Language:English
Published: London, United Kingdom ; San Diego, CA, United States ; Cambridge, MA, United States : Elsevier, Academic Press, an Imprint of Elsevier, [2025]
Edition:Seventh edition.
Subjects:
Online Access:Connect to the full text of this electronic book
Table of Contents:
  • Front Cover
  • Rosenberg's Molecular and Genetic Basis of Neurological and Psychiatric Disease
  • Copyright Page
  • The editors
  • Dedication
  • Contents
  • List of Contributors
  • About the editors
  • Foreword for the sixth edition
  • Prologue for the sixth edition
  • Introduction to the seventh edition
  • I. General concepts and tools
  • 1 Mendelian, non-Mendelian, multigenic inheritance, and epigenetics
  • Introduction
  • Mendelian traits
  • Mendel's laws
  • Chromosomes and genes
  • Mendelian inheritance
  • Molecular pathomechanisms of pathogenic variants
  • Locus and allelic heterogeneity
  • Factors that modify classic Mendelian inheritance patterns
  • New mutations, mosaicism, and somatic mutations
  • Penetrance and expressivity
  • Repeat expansion disorders
  • Non-Mendelian inheritance
  • Mitochondrial inheritance
  • Imprinting
  • Uniparental disomy
  • Chromosomal and genomic disorders
  • Aneuploidy
  • Isochromosomes
  • Translocations
  • Intrachromosomal rearrangements
  • Mechanisms for formation of chromosomal rearrangements
  • Nonallelic homologous recombination
  • Nonhomologous end-joining
  • Fork stalling and template switching/microhomology-mediated break-induced replication
  • How chromosomal rearrangements confer phenotypes
  • Multigenic inheritance
  • Multilocus pathogenic variation
  • Modifier genes
  • Mutational burden
  • Complex traits
  • Genetic features of complex traits
  • Genetic variation and complex traits
  • Examples of susceptibility genes for complex traits
  • Epigenetics
  • DNA methylation and hydroxymethylation
  • Histone modifications and higher-order chromatin remodeling
  • Noncoding RNA regulation
  • Assessing variation in the human genome
  • Cytogenetics
  • Next-generation sequencing
  • Conclusion
  • References
  • 2 Precision medicine in neurology
  • Introduction
  • Technologies contributing to precision medicine.
  • Metabolomics
  • Imaging
  • Wearable devices
  • Early precision medicine advancements
  • Initiation of precision medicine programs in the United States
  • Precision medicine results at individualized level (N-of-1)
  • Pharmacogenomics
  • Incorporation of precision diagnostics with targeted therapy
  • Summary
  • Acknowledgments
  • References
  • 3 Epigenomics of neurological disorders
  • Introduction
  • Types and mechanisms of epigenetic modifications
  • DNA modifications
  • Histone modifications
  • Long noncoding RNA roles in epigenetic changes
  • Epigenetic therapeutic strategies in neurological disorders
  • Alzheimer's disease
  • Modulating DNA methylation levels
  • Modulating histone modification
  • Long noncoding RNA-based strategies
  • BDNF upregulation
  • Dravet syndrome
  • Fragile X syndrome
  • Amyotrophic lateral sclerosis
  • Angelman syndrome
  • Rett syndrome
  • Spinal muscular atrophy
  • Conclusions
  • References
  • 4 What genes can and cannot do
  • Conceptual confusions in neurology and genetics
  • Genes are malleable
  • Biological causation: from and to genes and on to more important levels
  • What biological level(s) control the organism?
  • The crooked paths between genes and phenotypes
  • Abnormalities leading to normality
  • The generation of novel biology
  • Types of genes based on modifiability
  • Are misconceptions harmless?
  • Conclusion
  • Acknowledgments
  • References
  • 5 Genotype-phenotype considerations in neurogenetic disease
  • Introduction
  • Genotype
  • Phenotype
  • Genotype-phenotype correlation: definition and clinical use
  • Penetrance
  • Expressivity
  • Clinical heterogeneity
  • Complex disease and polygenic risk
  • Genotype-phenotype considerations for the neurogenetic evaluation
  • Conclusions
  • Funding
  • Conflict of interest
  • References
  • 6 Immunogenetics of neurological disease
  • Introduction.
  • Lessons from immunogenetics
  • Immune cell states
  • Major histocompatibility complex
  • Neurodegeneration and the immune system
  • Neurologic adverse events from immunotherapy: role of immunogenetics
  • Immunosenescence
  • Immunogenetics and the future of neurologic disease
  • References
  • Further reading
  • 7 Pharmacogenomic approaches to the treatment of sporadic Alzheimer's disease
  • Genetic risk factors and sporadic Alzheimer's disease
  • Genetic risk factors, cholinergic dysfunction, and Alzheimer's disease
  • APOE4 and cholinomimetic drugs in Alzheimer's disease
  • Experimental drugs and their relationship to the APOE4 genotype
  • Acetylcholinesterase and butyrylcholinesterase genetic variants in dementia
  • Pharmacogenomics of adverse side effects
  • Acknowledgments
  • References
  • 8 Application of mouse genetics to human disease: generation and analysis of mouse models
  • Creating mouse models
  • CRISPR/Cas9
  • Transgenesis
  • Gene targeting
  • Random mutagenesis
  • Phenotypic analysis of mouse models
  • Summary
  • References
  • 9 DNA sequencing and other methods of exonic and genomic analyses
  • DNA sequencing technologies
  • Application of next-generation sequencing to elucidating Mendelian-trait diseases
  • Application of next-generation sequencing to elucidating molecular basis of diseases with Mendelian trait
  • Application of next-generation sequencing to discovery of causative genes (positional cloning)
  • Search for de novo mutations based on whole-exome sequencing/whole-genome sequencing analyses of trios
  • Application of next-generation sequencing to elucidating molecular basis of complex-trait diseases
  • Application of next-generation sequencing to clinical sequencing
  • Other methods of exonic and genomic analysis
  • New technologies for haplotyping
  • Detection of low-frequency alleles
  • References.
  • 10 Association, cause, and causal association. Revision 2: playing the changes
  • Considerations
  • Learning from infectious disease
  • Causal "guidelines" and observational versus experimental designs
  • A path forward and artificial intelligence
  • The progression of complexity into public health
  • References
  • 11 Adeno-associated virus-mediated gene therapy in central nervous system genetic disorders
  • Introduction
  • Part I: development of adeno-associated virus as a central nervous system gene transfer vector
  • Overview of adeno-associated virus capsid structure and functions
  • Adeno-associated virus capsid engineering for central nervous system gene therapy
  • Methods used to engineer adeno-associated virus
  • Part II: development of AAV-mediated gene therapy for CNS diseases
  • Types of gene therapy
  • Expression cassette design elements
  • Adeno-associated virus applications based on central nervous system disorder categories
  • Preclinical safety and efficacy evaluation
  • Part III: clinical translation, milestones, and challenges
  • Historical context and current landscape of adeno-associated virus-central nervous system gene therapy
  • Future challenges to clinical advancement of adeno-associated virus-central nervous system gene therapy
  • Conclusion
  • Acknowledgments
  • References
  • 12 Genomics of human neurological disorders
  • "-Omics"
  • Technology
  • Human variation
  • Clinical impact of human variation
  • Comparative genomics
  • Functional genomics
  • Noncoding elements
  • Single cell transcriptomics
  • Applying human genomics to understanding disorders of the nervous system
  • References
  • 13 CRISPR/Cas9-based genetic engineering for translational research in neurological disorders
  • Introduction
  • CRISPR and its working mechanisms
  • DNA cleavage via conventional CRISPR/Cas9 in neurological disorders.
  • The expanding family of CRISPR effectors and toolkits for gene editing
  • Base editing in neurological disorders
  • CRISPR-mediated transcriptional activation in neurological disorders
  • CRISPR-mediated transcriptional repression in neurological disorders
  • CRISPR screening and functional genomics for neurological disorders
  • RNA editing using CRISPR/Cas 13 for neurological disorders
  • Challenges toward a fruitful translation of CRISPR technologies for clinical neurology
  • Concluding remarks
  • Acknowledgments
  • References
  • 14 Neural cells derived from pluripotent stem cells and directly induced from somatic cells
  • Introduction
  • Stem cell-based regenerative therapy of spinal cord injury
  • Direct induction of neural stem cells from somatic cells
  • Direct induction of neurons from somatic cells
  • References
  • 15 Neuroimaging in dementia
  • Neuroimaging technologies
  • Diffusion magnetic resonance imaging
  • Task-free functional magnetic resonance imaging
  • Arterial spin labeling
  • Alzheimer's disease
  • Clinical manifestation of Alzheimer's disease
  • Pathologies underlying Alzheimer's disease
  • Imaging in Alzheimer's disease
  • Amyloid imaging
  • Fluorodeoxyglucose-positron emission tomography imaging
  • Tau imaging
  • Magnetic resonance imaging
  • Dementia with Lewy bodies
  • Clinical manifestation of dementia with Lewy bodies
  • Pathologies underlying dementia with Lewy bodies
  • Imaging in dementia with Lewy bodies
  • Amyloid imaging
  • Fluorodeoxyglucose-positron emission tomography
  • Magnetic resonance imaging
  • Frontotemporal dementia
  • Clinical manifestation of frontotemporal dementia
  • Pathology underlying frontotemporal dementia
  • Imaging in frontotemporal dementia
  • Amyloid imaging
  • Fluorodeoxyglucose-positron emission tomography and magnetic resonance imaging.