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

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
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