Genomics, circuits, and pathways in clinical neuropsychiatry / edited by Thomas Lehner, Bruce L. Miller, Matthew W. State.

Format:

Book

Contributor:

Lehner, T. (Thomas), editor.

Miller, Bruce L., editor.

State, Matthew W., editor.

Language:

English

Subjects (All):

Neuropsychiatry.

Physical Description:

1 online resource (798 pages)

Place of Publication:

Amsterdam, Netherlands : Academic Press, 2016.

Summary:

This foundational work comprehensively examines the current state of the genetics, genomics and brain circuitry of psychiatric and neurological disorders. It consolidates discoveries of specific genes and genomic regions associated with these conditions, the genetic and anatomic architecture of these syndromes, and addresses how recent advances in genomics are leading to a reappraisal of the biology underlying clinical neuroscience. In doing so, it critically examines the promise and limitations of these discoveries toward treatment, and to the interdisciplinary nature of understanding brain and behavior. Coverage includes new discoveries regarding autism, epilepsy, intellectual disability, dementias, movement disorders, language impairment, disorders of attention, schizophrenia, and bipolar disorder. Genomics, Circuits, and Pathways in Clinical Neuropsychiatry focuses on key concepts, challenges, findings, and methods in genetics, genomics, molecular pathways, brain circuitry, and related neurobiology of neurologic and psychiatric disorders.- Provides interdisciplinary appeal in psychiatry, neurology, neuroscience, and genetics- Identifies key concepts, methods, and findings- Includes coverage of multiple disorders from autism to schizophrenia- Reviews specific genes associated with disorders- Discusses the genetic architecture of these syndromes- Explains how recent findings are influencing the understanding of biology- Clarifies the promise of these findings for future treatment

Contents:

Front Cover

Genomics, Circuits, and Pathways in Clinical Neuropsychiatry

Copyright

Contents

List of Contributors

Preface

I - The Genome Tools and Methods

1 - The Newly Emerging View of the Genome

INTRODUCTION

CONCEPTUALIZING DNA

INFORMATION FLOW IN BIOLOGICAL SYSTEMS

KEY DEFINITIONS

Cis and Trans

Gene

Transcript

High-Throughput Sequencing

THE GENOME (DNA)

VISUALIZING THE GENOME

LARGE-SCALE STRUCTURES IN THE GENOME

Telomeres

Subtelomeres

Centromeres

SMALL-SCALE STRUCTURES IN THE GENOME

Protein-Coding Genes

Promoters

Untranslated Regions

Exons

Introns

Splice Sites

Protein-Coding Sequence

Noncoding Transcripts/Genes

Pseudogenes

Long Noncoding RNAs

Small Noncoding RNAs

Circular RNAs

Enhancers

Silencers

Insulators

Repetitive Elements

DNA Transposons

Short Interspersed Nuclear Elements

Long Interspersed Nuclear Elements

Long Terminal Repeat Retrotransposons

MULTIPLE ROLES

VARIATION IN THE GENOME

Entire Chromosomes

Structural Variation

Insertions and Deletions

Single-Nucleotide Variants

Loss-of-Function Variants

ETHNICITY AND POPULATION FREQUENCY OF VARIANTS IN THE GENOME

VARIATION IN COMPLEX AND MENDELIAN DISORDERS

CHROMATIN (DNA, RNA, AND PROTEIN) AND EPIGENETICS

Chromatin State

Heterochromatin

Euchromatin

DNA Methylation

Histone Proteins

Chromatin Remodelers

Transcription Factors

Cofactors

Elongation Factors

Cohesins

REGULATORY COMPLEXES

Preinitiation Complex (PIC)

General Transcription Factors

RNA Polymerase II

Mediator (Coactivator)

Proximal Promoter-Pausing Complexes

Elongation Complex

TRANSCRIPTION (RNA)

POSTTRANSCRIPTIONAL MRNA MODIFICATIONS

Epitranscriptome.

RNA Editing

RNA Processing

TRANSLATION

POSTTRANSLATIONAL MODIFICATIONS

SUMMARY

REFERENCES

2 - Contribution of Genetic Epidemiology to Our Understanding of Psychiatric Disorders

BACKGROUND: EPIDEMIOLOGY

Contributions to Psychiatry

Genetic Epidemiology

Family Studies

Twin Studies

Adoption Studies

GENETIC EPIDEMIOLOGY OF PSYCHIATRIC DISORDERS

Neurodevelopmental Disorders

Attention-Deficit Hyperactivity Disorder

Autism Spectrum Disorder

Schizophrenia

Eating Disorders

Mood Disorders

Anxiety Disorders: Panic Disorder

Obsessive-Compulsive Disorder

Substance Use Disorders

Summary

APPLICATIONS OF GENETIC EPIDEMIOLOGY IN MOLECULAR ERA

Study Designs and Samples

Genome-Wide Association Studies: Case-Control Studies

Whole Genome/Exome Sequencing of Case-Control Studies

Population Registries and Biobanks

Statistical Approaches to Estimate Genetic Influence

Phenotypes: Moving Beyond Dichotomous Classification

Phenotypic Boundaries

Use of Endophenotypes for Classification

Computational Phenotype Analysis

Incorporation of Environmental Factors

Combining Genetic and Environmental Factors

Team Science

3 - Natural Selection and Neuropsychiatric Disease: Theory, Observation, and Emerging Genetic Findings

EPIDEMIOLOGY OF NEUROPSYCHIATRIC DISEASE

THEORETICAL CONSIDERATIONS

HYPOTHESIS TESTING: EPIDEMIOLOGY AND EMERGING GENETIC DATA

MENDELIAN RANDOMIZATION AND POLYGENIC RISK

DE NOVO MUTATION AND MUTATION-SELECTION BALANCE

CONCLUSIONS

4 - Genome Tools and Methods: Rare Genetic Variation

RARE VARIANTS IN PSYCHIATRIC DISEASE

GENETIC VARIATION

MODERN TECHNOLOGIES FOR DISCOVERY OF RARE VARIANTS.

MICROARRAY TECHNOLOGY AND LARGE-SCALE COPY NUMBER VARIANTS IN NEURODEVELOPMENTAL AND NEUROPSYCHIATRIC DISEASE

COPY NUMBER VARIANT STUDIES OF DISEASE

STUDIES OF DE NOVO MUTATION IN TRIO FAMILIES

CASE-CONTROL STUDIES

ANALYSIS STRATEGIES

Genome

Pathways

Genes

SNVs

DETECTION OF RARE GENETIC VARIATION BY HIGH-THROUGHPUT SEQUENCING

Exome

Gene Panels

Whole Genome Sequencing

RARE GENETIC VARIATION IN NONCODING DNA: A NEW FRONTIER

RARE GENETIC VARIANTS AND THE POTENTIAL TO AFFECT CLINICAL CARE

5 - Neuroepigenomics and Human Disease

EPIGENETICS

EPIGENETICS IN NEUROBIOLOGICAL RESEARCH

THE GENOMIC CONTEXT OF TRANSCRIPTIONAL AND EPIGENETIC MECHANISMS

TRANSCRIPTIONAL AND EPIGENETIC REGULATORY MECHANISMS

EPIGENETIC PERTURBATION AND EPIGENOME-WIDE ASSAYS

CELL TYPE CHOICES IN NEUROEPIGENOMIC STUDIES

INTERACTION OF THE GENOME WITH THE EPIGENOME

EPIGENETICS MECHANISMS OF BRAIN DISEASES: GENERAL PRINCIPLES AND FUTURE DIRECTIONS

6 - Bioinformatics in Neuropsychiatric Genomics

WHAT IS BIOINFORMATICS?

DATABASES

METHODS

TOOLS

STANDARDS

LIST OF URLS

Core Genomic Databases and Portals

Genome Browsers

Genetic Variation

Gene Expression Resources

Programming Environments for Bioinformatics

Genetic Linkage, Association, and Variation Detection

Network and Pathway Analysis

Rare Variant Detection and Annotation

Identifiers, Ontologies, and Standards

Psychiatric/Neuroscience Projects

7 - Imaging Genomics and ENIGMA

POWER OF MRI

WHAT IS IMAGING GENOMICS?

The Endophenotype Concept and Biomarkers

MAPPING BRAIN DISEASES IN NEUROLOGY

MRI VERSUS CELLULAR MEASURES

MAPPING BRAIN DISORDERS: PSYCHIATRY

PSYCHIATRIC NEUROIMAGING EXPANDS WORLDWIDE

Meta-Analysis.

ENIGMA STUDIES OF BRAIN DISEASE

DEFUSING CONTROVERSY WITH META-ANALYSIS

IMAGING GENOMICS AND GENOME-WIDE ASSOCIATION STUDIES

GENETIC INFLUENCES ON THE BRAIN

GENES AND DISEASE RISK

MANHATTAN PLOTS

CANDIDATE GENES AND GENOME-WIDE ASSOCIATION STUDIES

GENOME-WIDE SIGNIFICANCE

FORMATION OF ENIGMA IN 2009

SURPRISES FROM IMAGING GENOMICS CONSORTIA

OTHER NEUROIMAGING METHODS

MULTIVARIATE IMAGING GENOMICS AND BIG DATA

SEARCHING THE BRAIN FOR GENE EFFECTS

Cooperative Machine Learning

ACKNOWLEDGMENTS

8 - Brain in a Dish: Stem Cell Technologies to Study Disorders of the Central Nervous System

GENERATING INDUCED PLURIPOTENT STEM CELLS

PROGRESS IN MODELING HUMAN CENTRAL NERVOUS SYSTEM PATHOLOGY: NEURODEVELOPMENTAL DISORDERS

RETT SYNDROME

FRAGILE X SYNDROME

ANGELMAN SYNDROME

TIMOTHY SYNDROME

CONTRIBUTION OF DIFFERENT CELL TYPES TO NEURODEVELOPMENTAL DISORDERS

THE NEXT STEP OF INDUCED PLURIPOTENT STEM CELLS: THREE-DIMENSIONAL CULTURES AND MINI-BRAINS

LIMITATIONS OF INDUCED PLURIPOTENT STEM CELL MODEL

GENOME EDITING: CREATING DISEASED EMBRYONIC STEM CELLS

DRUG DISCOVERY WITH INDUCED PLURIPOTENT STEM CELLS

9 - Association Strategies

COMMON VARIANTS

RARE VARIANTS

10 - Reconstructing Causal Network Models of Human Disease

MODELING BIOLOGICAL DATA

CAUSALITY AS A STATISTICAL INFERENCE

FROM ASSESSING CAUSAL RELATIONSHIPS AMONG TRAIT PAIRS TO PREDICTIVE GENE NETWORKS

Building From the Bottom Up or Top Down?

An Integrative Genomics Approach to Constructive Predictive Network Models

Integrating Genetic Data as a Structure Before Enhancing Causal Inference in the Bayesian Network Reconstruction Process.

Incorporating Other -Omics Data as Network Priors in the Bayesian Network Reconstruction Process

Elucidating the Complexity of Human Disease: From the Metabolic to the Psychiatric

APPLICATION OF PREDICTIVE NETWORK MODELS TO HIGH-THROUGHPUT SCREENING

CONCLUSION AND FUTURE DIRECTIONS

11 - Gene Networks in Neuropsychiatric Disease

RNA, PROTEIN, AND EPIGENETIC MOLECULAR LEVELS IN NEUROBIOLOGY

THE CHALLENGE OF SPATIAL AND TEMPORAL HETEROGENEITY IN THE CENTRAL NERVOUS SYSTEM

GENE NETWORKS PROVIDE A FRAMEWORK FOR NEUROBIOLOGICAL INTERPRETATION

GENE NETWORKS IN NEUROPSYCHIATRIC DISORDERS

Genome-Wide Approaches

Seed-Based Approaches

Protein-Protein Interaction Networks

Integrative Network Approaches

Themes From Cross-Method Comparisons

CONCLUSIONS AND FUTURE DIRECTIONS

12 - Somatic Mosaicism and Neurological Diseases

CORTICAL CLONAL ARCHITECTURE AND SOMATIC MUTATIONS

SOMATIC MUTATIONS IN NORMAL BRAIN

SOMATIC MUTATION IN NEUROLOGICAL DISEASE

``Brain-Only'' Somatic Mutations

``Second-Hit'' Mutations Produce Mosaicism

Neurodevelopmental Disorders Caused by Somatic Mutations

Neurological Diseases Caused or Modulated by Somatic Mutations

TYPES OF SOMATIC VARIANTS

Large-Scale Chromosomal Abnormalities

Copy Number Variants

TISSUE TYPE CONSIDERATIONS

TOOLS TO STUDY SOMATIC VARIATION IN THE BRAIN

Cytogenetics

Microarrays

Single-Cell Copy Number Analyses

Digital Droplet Polymerase Chain Reaction

Single-Nucleotide Variants, Including Insertions and Deletions

Sanger Sequencing

Subcloning Followed by Sanger Sequencing

Next-Generation Sequencing

Single-Cell Sequencing

Mass Spectrometry

CONCLUSION

REFERENCES.

II - A New Neuroanatomy.

Notes:

Includes bibliographical references at the end of each chapters and index.

Description based on print version record.

ISBN:

9780128005309

0128005300