Genome Plasticity in Health and Disease (Translational and Applied Genomics)

Description

Genome Plasticity in Health and Disease provides a fully up-to-date overview on genome plasticity and its role in human physiology and disease. Following an introduction to the field, a diverse range of chapters cover genomic and epigenomic analysis and the use of model organisms and genomic databases in studies. Specific molecular and biochemical mechanisms of genome plasticity are examined, including somatic variants, De Novo variants, founder variations, isolated populations dynamics, copy-number variations, mobile elements, DNA methylation, histone modifications, transcription factors, non-coding RNAs, telomere dynamics and RNA editing. Later chapters explore disease relevance for cancer, as well as cardiovascular, neuropsychiatric, inflammatory, and endocrine disease, and associated pathways for drug discovery. Genome Plasticity in Health and Disease Copyright Contributors 1 - Impact of genome plasticity on health and disease 1. Introduction 2. Plasticity of the human genome 3. Plasticity of the human genome and diseases 4. Conclusions Acknowledgments References 2 - Overview of the human genome 1. Introduction 1.1 Early history (1910–1971): Discovery of DNA 1.2 Rise of knowledge about DNA: 1950–1968 1.3 DNA sequencing: 1977 to the present 2. The human genome 2.1 Intervening sequences in the human genome 2.2 Noncoding sequences in human genes 2.3 Chromosomal organization 2.4 Tools used in genetics and genomics 2.5 DNA sequencing as a potent tool for the study of human genomes 3. Human genomics and the future of healthcare 3.1 Genomic medicine, precision medicine, and systems medicine 3.2 Relevance of the study of human genomics in clinical practice 4. Conclusion References 3 - Methods for epigenomic analyses: DNA methylation 1. Epigenetics 2. DNA methylation 3. DNA treatment prior to DNA methylation analysis 3.1 Fragmentation with restriction endonucleases 3.2 Affinity enrichment 3.3 Bisulfite conversion 4. Methods for analysis of DNA methylation 4.1 Global DNA methylation profiling 4.2 Locus-specific assays 4.3 Genome-wide DNA methylation mapping 4.3.1 Microarray-based methods 4.3.2 NGS-based methods 5. Challenges 6. Conclusions References 4 - Genomic databases 1. Introduction 2. Reference genomes, genes, and annotations 3. Searching genomic databases 3.1 Genome browsers 3.2 Karyotype bands and chromosomal coordinates 3.3 Sequences and motifs 3.4 Multiple and complex genomic database searches 3.5 Application programming interfaces 4. Genomic variations 5. Perspectives Acknowledgments Conflict of interest statement References 5 - Genomic variability: germline, somatic, and de novo variants 1. Introduction 2. Overview of germline variation and genetic architecture 3. De novo mutations 4. Somatic mosaicism 5. Conclusions References 6 - Founder variations in isolated populations 1. What is a population isolate? 2. Founder effects and linkage disequilibrium 3. Genetic risk variant detection in isolated populations 3.1 Identification of founder variations using linkage disequilibrium 3.2 Validity of findings from isolated populations 4. Mendelian disorders in isolated populations 4.1 Diastrophic dysplasia 4.2 Progressive myoclonus epilepsy 4.3 Chloride diarrhea 5. Complex disorders in isolated populations 6. Conclusion References 7 - DNA methylation 1. Introduction 2. Mechanisms of DNA methylation and demethylation 3. DNA methylation in human diseases 3.1 Cancer 3.2 Aging 3.3 Metabolic disorders 3.4 Neurological disorders 4. Quantitative detection of DNA methylation and its derivatives 4.1 Chemical derivatization coupled with mass spectrometry 4.2 Enrichment pretreatment coupled with LC-MS/MS 4.3 Single molecule, real-time DNA sequencing 5. Concluding remarks Acknowledgments Conflict of interest statement References 8 - Chromatin, histones, and histone modifications in health and disease 1. Introduction 2. Phenotypic status of plasticity 3. Epigenetics phenomenon 4. Epigenetic factors in plasticity and disease 4.1 Histone variants 4.2 Histone posttranslational modifications 4.2.1 Histone acetylation and deacetylation 4.2.2 Histone methylation and diseases 4.2.3 Histone phosphorylation 4.2.4 Histone ubiquitination 4.2.5 Histone citrullination and histone deaminases 4.2.6 Histone crotonylation 5. Epigenetics, nutrition, and disease 6. Perspective and concluding remarks Declarations References 9 - Networks of transcription factors 1. Introduction 1.1 Transcriptional regulation and gene expression 1.2 Perturbation experiment approaches to transcriptional networks 1.3 Transcription factor regulatory networks 2. Transcription factor-binding site prediction 2.1 The MotEvo approach 2.2 The iRegulon approach 3. Probabilistic transcription factor networks 3.1 The ARACNe–MARINa information theoretical approach 3.1.1 Construction of the ARACNe transcription factor network 4. Regulation by transcription factors and beyond 4.1 Multiomic approaches to transcription factor-mediated regulation 5. Concluding remarks References 10 - Centromere and telomere dynamics in humans 1. Centromeres 2. Centromeres are regions of highly specialized chromatin 3. The evolution of centromeric DNA 4. Centromeric nucleosome 5. Centromeric transcription 6. Centromere genomics 7. Cohesin 8. Centromere abnormalities 9. Telomeres 10. The telomerase enzyme 11. Regulation of the function of telomerase 12. Transcriptional regulation of TERT 13. Posttranslational regulation of TERT 14. Epigenetic regulation 15. Environmental factors 16. Telomere length 17. Determinants of telomere length 18. Telomere-targeted therapy 19. Future perspectives References 11 - Genome plasticity and cardiovascular diseases 1. Genetics of cardiovascular diseases 2. Genome-wide association studies 3. Epigenetics and CVD phenotype variability References 12 - Genome plasticity and neuropsychiatric disorders 1. Introduction 2. Neuropsychiatric genomics 3. Molecular genomics of Parkinson's disease 4. MicroRNAs and Alzheimer's disease Acknowledgments References 13 - Genome plasticity and endocrine diseases 1. Introduction of genome research in medicine 2. Introduction of endocrine diseases 3. Genome plasticity and T2DM 3.1 Germline, somatic, and de novo variants in T2DM 3.2 Copy number variations in T2DM 3.3 DNA methylation in T2DM 3.4 Noncoding RNA and RNA editing in T2DM 3.5 Centromere and telomere dynamics in T2DM 3.6 Glycosylation in T2DM 4. Genome plasticity and AITD 4.1 Germline, somatic, and de novo variants in AITD 4.2 DNA methylation in AITD 5. Conclusion Author disclosure statement Acknowledgments References Further reading 14 - Implications of genome plasticity for drug development 1. Drug development 1.1 Preclinical research 1.2 Clinical research (phases I, II, and III) 1.3 Drug submission and approval 1.4 Postmarketing 1.5 Exome studies and drug response 2. Epigenetic mechanisms in pharmacogenetics 2.1 Potential role of microRNAs in drug response 2.2 Insights into DNA methylation in drug response 2.3 Histone modifications and drug response 2.4 Epigenetic drugs 3. New molecular techniques in drug development 3.1 Introduction to gene therapy 3.1.1 Gene addition/gene therapy 3.1.2 Gene editing 3.2 Ethics of germline genomic edits 3.2.1 Gene silencing 3.2.1.1 Antisense oligonucleotides 3.2.1.2 Epigenetic alterations 4. Conclusion References Index A B C D E F G H I J K L M N O P Q R S T U V W X Y Z